80 results on '"Rudovich N"'
Search Results
2. Plasma adiponectin in heart failure with and without cachexia: Catabolic signal linking catabolism, symptomatic status, and prognosis
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Szabó, T., Scherbakov, N., Sandek, A., Kung, T., von Haehling, S., Lainscak, M., Jankowska, E.A., Rudovich, N., Anker, S.D., Frystyk, J., Flyvbjerg, A., Pfeiffer, A.F.H., and Doehner, W.
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- 2014
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3. Regulation of the clock gene expression in human adipose tissue by weight loss
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Pivovarova, O, Gögebakan, Ö, Sucher, S, Groth, J, Murahovschi, V, Kessler, K, Osterhoff, M, Rudovich, N, Kramer, A, and Pfeiffer, A F H
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- 2016
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4. Acarbose treatment enhances mid-regional pro-atrial natriuretic peptide concentrations in non-diabetic individuals: further evidence for a common cardiometabolic pathway?
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Rudovich, N., Pivovarova, O., Traberth, A., Sparwasser, A., Weickert, M. O., Bernigau, W., Birkenfeld, A. L., Arafat, A. M., Bergmann, A., and Pfeiffer, A. F. H.
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- 2012
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5. P584PPARg and natriuretic peptides (NP) pathways are altered in adipose tissue from heart failure patients/ mesenchymal stromal cells (MMSC) as a tool to study cardiovascular metabolic disorders in vitro
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Revittser, A, Pivovarova, O, Rudovich, N, Pfeiffer, AFH, Shlyakhto, E, and Dmitrieva, R
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- 2014
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6. Glucose inhibits the insulin-induced activation of the insulin-degrading enzyme in HepG2 cells
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Pivovarova, O., Gögebakan, Ö., Pfeiffer, A. F. H., and Rudovich, N.
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- 2009
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7. Association of insulinase gene polymorphisms with type 2 diabetes mellitus in patients from the Moscow population
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Slominsky, P. A., Pivovarova, O. V., Shadrina, M. I., Artem’eva, A. V., Pfaipffer, F. G., Rudovich, N. N., Agadghanyan, S. E., Pronin, V. S., and Limborska, S. A.
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- 2009
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8. Arabinoxylan consumption decreases postprandial serum glucose, serum insulin and plasma total ghrelin response in subjects with impaired glucose tolerance
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Garcia, A L, Otto, B, Reich, S-C, Weickert, M O, Steiniger, J, Machowetz, A, Rudovich, N N, Möhlig, M, Katz, N, Speth, M, Meuser, F, Doerfer, J, Zunft, H-J F, Pfeiffer, A H F, and Koebnick, C
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- 2007
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9. Impact of cereal fibre on glucose-regulating factors
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Weickert, M. O., Mohlig, M., Koebnick, C., Holst, J. J., Namsolleck, P., Ristow, M., Osterhoff, M., Rochlitz, H., Rudovich, N., Spranger, J., and Pfeiffer, A. F. H.
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- 2005
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10. GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE INFLUENCES PLASMA CONCENTRATIONS OF LONG-CHAIN FATTY ACIDS IN HUMAN OBESITY: A PILOT CLAMP STUDY
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Rudovich, N., Pivovarova, O., Dörmann, P., Erban, A., Gögebakan, Ö., Nauck, M., Nikiforova, V. J., and Pfeiffer, A. F.H.
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- 2011
11. Arabinoxylan fibre consumption improved glucose metabolism, but did not affect serum adipokines in subjects with impaired glucose tolerance
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Garcia, A. L., Steiniger, J., Reich, S. C., Weickert, M. O., Harsch, I., Machowetz, A., Mohlig, M., Spranger, Joachim, Rudovich, N. N., Meuser, F., Doerfer, J., Katz, N., Speth, M., Zunft, Hans-Joachim Franz, Pfeiffer, Andreas F. H., and Koebnick, Corinna
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Institut für Ernährungswissenschaft ,ddc:610 ,hormones, hormone substitutes, and hormone antagonists - Abstract
The consumption of arabinoxylan, a soluble fibre fraction, has been shown to improve glycemic control in type 2 diabetic subjects. Soluble dietary fibre may modulate gastrointestinal or adipose tissue hormones regulating food intake. The present study investigated the effects of arabinoxylan consumption on serum glucose, insulin, lipids, leptin, adiponectin and resistin in subjects with impaired glucose tolerance. In a randomized, single-blind, controlled, crossover intervention trial, 11 adults consumed white bread rolls as either placebo or supplemented with 15g arabinoxylan for 6 weeks with a 6-week washout period. Fasting serum glucose, insulin, triglycerides, unesterified fatty acids, apolipoprotein A1 and B, adiponectin, resistin and leptin were assessed before and after intervention. Fasting serum glucose, serum triglycerides and apolipoprotein A-1 were significantly lower during arabinoxylan consumption compared to placebo (p = 0.029, p = 0.047; p = 0.029, respectively). No effects of arabinoxylan were observed for insulin, adiponectin, leptin and resistin as well as for apolipoprotein B, and unesterified fatty acids. In conclusion, the consumption of AX in subjects with impaired glucose tolerance improved fasting serum glucose, and triglycerides. However, this beneficial effect was not accompanied by changes in fasting adipokine concentrations.
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- 2006
12. Glucose-dependent insulinotropic polypeptide reduces fat-specific expression and activity of 11β-hydroxysteroid dehydrogenase type 1 and inhibits release of free fatty acids.
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Gögebakan O, Andres J, Biedasek K, Mai K, Kühnen P, Krude H, Isken F, Rudovich N, Osterhoff MA, Kintscher U, Nauck M, Pfeiffer AF, Spranger J, Gögebakan, Özlem, Andres, Janin, Biedasek, Katrin, Mai, Knut, Kühnen, Peter, Krude, Heiko, and Isken, Frank
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Glucose-dependent insulinotropic polypeptide (GIP) has been suggested to have direct effects on nonislet tissues. GIP also reportedly increased glucose uptake and inhibition of lipolysis in adipocytes after inhibition of the intracellular cortisone-cortisol shuttle 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). We here analyzed whether GIP modifies lipid metabolism and further elucidated the relation between GIP, 11β-HSD1, and fatty acid metabolism. GIP reduced activity of 11β-HSD1 promoter constructs and the expression and activity of 11β-HSD1 in differentiated 3T3-L1 adipocytes in a time- and dose-dependent fashion. This was paralleled by a reduction of free fatty acid (FFA) release and a reduced expression of key enzymes regulating lipolysis in adipose tissue. Preinhibition of 11β-HSD1 completely abolished GIP-induced effects on FFA release. To investigate the acute effects of GIP in humans, a randomized clinical trial was performed. GIP lowered circulating FFAs compared with saline control and reduced expression and ex vivo activity of 11β-HSD1 and adipose triglyceride lipase expression in subcutaneous fat biopsies. Our data suggest that GIP reduces FFA release from adipose tissue by inhibition of lipolysis or by increased reesterification. This process appears to depend on a modification of 11β-HSD1 activity. In general, the presented data support that GIP has direct and insulin-independent effects on adipose tissue. [ABSTRACT FROM AUTHOR]
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- 2012
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13. Changes in dominant groups of the gut microbiota do not explain cereal-fiber induced improvement of whole-body insulin sensitivity
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Weickert Martin O, Arafat Ayman M, Blaut Michael, Alpert Carl, Becker Natalie, Leupelt Verena, Rudovich Natalia, Möhlig Matthias, and Pfeiffer Andreas FH
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cereal fiber ,whole-body insulin sensitivity ,gut microbiota ,short chain fatty acids (SCFA) ,colonic fermentation ,Nutrition. Foods and food supply ,TX341-641 ,Nutritional diseases. Deficiency diseases ,RC620-627 - Abstract
Abstract Background Diets high in cereal-fiber (HCF) have been shown to improve whole-body insulin sensitivity. In search for potential mechanisms we hypothesized that a supplemented HCF-diet influences the composition of the human gut microbiota and/or biomarkers of colonic carbohydrate fermentation. Methods We performed a randomized controlled 18-week intervention in group-matched overweight participants. Fecal samples of 69 participants receiving isoenergetic HCF (cereal-fiber 43 g/day), or control (cereal-fiber 14 g/day), or high-protein (HP, 28% of energy-intake, cereal-fiber 14 g/day), or moderately high cereal fiber/protein diets (MIX; protein 23% of energy-intake, cereal-fiber 26 g/day) with comparable fat contents were investigated for diet-induced changes of dominant groups of the gut microbiota, and of fecal short-chain fatty-acids (SCFA) including several of their proposed targets, after 0, 6, and 18-weeks of dietary intervention. In vitro fermentation of the cereal fiber extracts as used in the HCF and MIX diets was analyzed using gas chromatography. Diet-induced effects on whole-body insulin-sensitivity were measured using euglycaemic-hyperinsulinemic clamps and re-calculated in the here investigated subset of n = 69 participants that provided sufficient fecal samples on all study days. Results Gut microbiota groups and biomarkers of colonic fermentation were comparable between groups at baseline (week 0). No diet-induced differences were detected between groups during this isoenergetic intervention, neither in the full model nor in uncorrected subgroup-analyses. The cereal-fiber extract as used for preparation of the supplements in the HCF and MIX groups did not support in vitro fermentation. Fecal acetate, propionate, and butyrate concentrations remained unchanged, as well as potential targets of increased SCFA, whereas valerate increased after 6-weeks in the HP-group only (p = 0.037). Insulin-sensitivity significantly increased in the HCF-group from week-6 (baseline M-value 3.8 ± 0.4 vs 4.3 ± 0.4 mg·kg-1·min-1, p = 0.015; full model 0-18-weeks, treatment-x-time interaction, p = 0.046). Conclusions Changes in the composition of the gut microbiota and/or markers of colonic carbohydrate fermentation did not contribute explaining the observed early onset and significant improvement of whole-body insulin sensitivity with the here investigated HCF-diet. Trial registration This trial was registered at http://www.clinicaltrials.gov as NCT00579657
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- 2011
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14. P584 PPARg and natriuretic peptides (NP) pathways are altered in adipose tissue from heart failure patients/ mesenchymal stromal cells (MMSC) as a tool to study cardiovascular metabolic disorders in vitro.
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Revittser, A, Pivovarova, O, Rudovich, N, Pfeiffer, AFH, Shlyakhto, E, and Dmitrieva, R
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NATRIURETIC peptides ,HEART failure ,MESENCHYMAL stem cells ,STROMAL cells ,ADIPOSE tissues ,CARDIOVASCULAR diseases ,METABOLIC disorders ,IN vitro studies - Abstract
Background and aim: heart failure (HF) is associated with an increase of systemic and myocardial insulin resistance, decrease of metabolism of fatty acids (FA) and a shift toward glucose for ATP generation. The defects in FA oxidation, mitochondrial dysfunction and/or chronic activation of NP system are proposed as the possible triggers of development of metabolic disorder in HF; however the exact mechanisms of these disorders are largely unknown. Our goal was to investigate the alterations in PPAR and NP pathways in adipose tissue from heart failure patients using cellular in vitro models.Methods: in vitro adipodenic differentiation of previously characterized adipose (AD) and bone marrow (BM) derived MMSC from healthy donors (HD; n=4) and HF patients (n=4) was done. The stimulation of adipogenesis performed as widely described. Gene expression was measured by Q-PCR at days 0, 4, 8 and 11 after stimulation.Results: expression of genes responsible for energy metabolism, glucose utilization, and NP pathway during differentiation of MMSC from AD of HF and HD is demonstrated in Table 1. Dynamics of expression of these genes during differentiation of BMMSC were very similar.Conclusion: Our data indicate that in HF both, PPAR- and NP- dependent pathways as well as glucose utilization are altered in adipose of different origin. Results are in a good accordance with data from clinical and animal studies demonstrating that fetal gene program is reactivated in failing heart. We have proved here that adipose culture system from cardiovascular patients is a relatively easy available model to study mechanisms of cardiovascular metabolic disorders in vitro, and a good tool to test how adipose tissue responds at molecular levels to different physiological and pharmacological interventions.Table 1Healthy DonorHeart FailureControlDay 4Day 8Day 11ControlDay 4Day 8Day 11PPARg6+2,162+19*36+10*44+12*4,3+1,76,7+2,7(**)4,5+1,3(**)2,3+1,7(**)Pgc1a2,7+0,7229+58*68+25*34+10*3,1+118+2,3*/(**)7,9+2(**)2,1+1(**)a2p21,6+0,3210312+70541*72347+30338*36181+14212*5,6+3,239101+16053*20299+7330*537+376GLUT42,9+0,64,8+1,137+13*32+12*12+42,9+0,75,7+1,6(**)1,3+0,3(**)NPRA3,8+1,1312+46*91+29*47+15*3,2+0,536+10*/(**)9,2+4,9(**)2,2+1,3(**)NPRC3,3+1,239+11*20+2*12+1*6,7+1,131+5*8,2+1,4(**)3,6+1,8(**)*p<0,05 vs control; *p<0,05 vs control; (**)p<0,05 vs HD [ABSTRACT FROM AUTHOR]
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- 2014
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15. 40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004
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S. Artigas, A V Dreval, Mark I. McCarthy, C Watson, Peter H. Bennett, M Quint, Y Ikeda, E Alpert, F Schiele, H Sekihara, Erik Gylfe, P Lowe, J Kuhlmann, Alain Golay, V Longo, Shahidul Alam Khan Akm., L G Mantovani, M Zawodniak-Szalapska, G Winkler, T Harrity, L Virág, U Johne, Kuo S-W., Linda C Tapsell, J Rodriguez, Michel Komajda, K Kankova, Carole A. Cull, M Sporna, E Estilles, U Ribel, M C Spruce, E Buzzigoli, T Prazak, J K McLaughlin, M K Lingohr, M Lim, F Calara, A Siebenhofer, G Meregalli, Roberto Anichini, A D Baron, R Kurashvili, P C Butler, G I Fantus, T. E. De Gooyer, Park Y-M., R. Walther, S Heinrich, Agnieszka Zawiejska, S Mukherjee, Nikolaos Papanas, G Wong, Ian D. Caterson, David M. Maahs, Shuichi Kaneko, Alexandra E. Butler, Francisco Javier Ampudia-Blasco, O N Kong, Attali J-R., C A Hedman, K Oshinyemi, Nicolle Müller, I C Cranston, N Okumus, M V Vlaiculescu, Balasubramanian Ravikumar, W W Cheatham, K Mukasa, K B Biswas, Annunziata Lapolla, Phil McEwan, G Mader, Gilles Chassot, Dragi Anevski, Werner A. Scherbaum, M Donath, C Hesselmann, R A Gandhi, David E. Moller, Ezio Bonifacio, C Garcia, V Ifandi, P Hornnes, Nieuwenhoven Fav., C Puech, S Pérez-Del-Pulgar, Kim S-R., G Hines, C Rubio Terrés, Michael Gaster, N. Hosszufalusi, A Scholze, Andrew A. Young, Stavros Liatis, F Hariri, S Tan, Paul Valensi, Allan E. Karlsen, J Kim, E. Moberg, J Kaiser, L Berman, G Nelson, A Altkrüger, P Kothare, D B Cook, S Doran, G. van Dijk, Shahnaz Shahinfar, Kim C-S., P Stahl, M Manousaki, S Sigrist, S K Lim, M. P. Stern, A Guberti, C Rezzani, J McKenney, Karl Thomaseth, Sofia Carlsson, M Julia, R Brillante, I Rubesova, T Darkow, E Matsumoto, Wendy M. Macfarlane, M Di Martino, G Bardini, Rossella Menghini, D Duhot, E Farcasiu, Annalisa Natalicchio, I Lindner, J Buvat, Christian L. Brand, Harry Dorchy, Iwona Pietrzak, Z T Luo, P Home, M Ekelund, Jesper Gromada, Kristine Færch, F Piarulli, H Kim, R Mentel, Zsuzsanna K. Zsengellér, Dullaart Rpf., Anton Luger, Thomas A. Pearson, V Manicardi, P Rösen, Feng Y-M., R Morganti, Lars Hansen, Demuth H-U., Haruo Kasai, A Shostak, Rudi Steffensen, G Taylor, Markolf Hanefeld, C Santini, E Hamaguchi, Roberto Miccoli, F Storms, M Cooper, Y Lee, Allison E. Aiello, P Smith, T Suehiro, K Treece, M Waluś, Timothy A Welborn, Simone Baltrusch, E Kontela, S Chai, J Crean, H Yokoyama, Johan G. Eriksson, Rafael Hernández Hernández, J Rodríguez-Saldaña, M P Tornero, G Formoso, D. Lovell, E Bingham, A Mylonakis, M Manteghetti, D Fedele, Antonio Martín-Duce, Ralph A. DeFronzo, D Salcedo, Kurt Højlund, Antonio Petrone, Sheu Whh., C Gutierrez, Flavia Pricci, S Kurita, Z G Abbas, M M Benedetti, Philippe A. Halban, Daniel J. Cox, O Ljungkvist, Justine Davies, J Palsgaard, Lars Sjöström, E Bosi, L Janin-Manificat, W. F. Kelly, M. Fernandez, E Colak, O V Mulyarchik, B Kronshage, F Lang, M Erfurth, Takashi Kadowaki, N Jendrike, U Walter, J Wishart, Y. Neye, D Kim, N Furuhashi, M Barsotti, D Florow, L Ke, L Borgquist, N C Jackson, Ffolliott M. Fisher, V Baskar, K Yoshioka, Bryan A. Wolf, G Chabrier, R Skoumal, Livio Luzi, H Kose, I Pharisien, B. Klein, H Winiarska, M C Johnson, L Griffiths, Nonna Kravchun, C Combe, Baptist Gallwitz, J Zdychova, L Skorda, Jorma Ilonen, W Gao, I N Steen, A Terrinoni, P D Ambery, W Kern, C M Kusminski, Cho M-H., Paolo Pozzilli, Louise G. Grunnet, E Schönle, David R Matthews, Robert W. Taylor, Y Cohen, Kim H-S., M P Eccles, N B Tutuncu, D McDowell, Richard M. Bergenstal, K Takamatsu, T Steiner, Jaan Palgi, Valdemar Grill, N Niculescu, G Federici, S Lehto, P. M. McKeigue, M Barone, Michael E. Trautmann, S Smirnov, J Mannion, M Eto, C Rousseau, M Conti, C S Ernest, Antonio Ceriello, D H Schweitzer, Jung E-D., Andreas Festa, Avijit Lahiri, A Shepelkevich, A Murro, A Kollmann, Jonathan R.S. Arch, R Landgraf, Son H-Y., I Engelsberger, E Agardh, S Rodríguez-Mulero, P J Kraml, K Lee, D. F. Du Toit, E Kim, G Fadini, Williams Ajk., Philip Home, M B Antcieferov, C Perlemoine, D Perrea, Song X-L., D Ruggieri, Krister Bokvist, Heidi Sørensen, Bilbao, G Yoshino, J P Taylor, Shen H-M., S M Furier, R Urquhart, J Wohlgelernter, Jianping Weng, T. Baba, Q Hong, C Silva, Castaigne J-P., M Felaco, X X Zhang, M Jaroň, Milla Rosengård-Bärlund, J G Papp, Toshio Miyata, Lervang H-H., Park M-K., I Kinalska, A Long, Oomen Phn., N Kogawa, Ippolita Patrizia Patera, S. Karadeniz, Dinesh Selvarajah, D S Chung, A Wensaas, Richard Imrich, M Recasens, J Ruxer, O Buchea, E Wilpart, S P Stepanenko, Le Ttd., H Ohgawara, Mariaconsuelo Valentini, A Mondok, M Peltonen, Marianne O. Larsen, K Chatzianagnostou, Agneta Ståhle, A L Ferrari, L Bordier, F Maingrette, A Matsuda, G Vukomanovic, Jakob D. Wikstrom, T Yamakita, E Gorostiaga, J Jin, B Gopalan, Heinz Drexel, S Hewitt, Rury R. Holman, C Dieterle, T L Ruchti, N Asatiani, M Sidira, A Iezzi, A J Sommerfield, D Châtenet, M L Olsen, R Bergemann, C Koehler, T L Kuraeva, B Balas, Christian Berne, E Santos-Mazo, G Smith, A Siejka, R Kožnarová, A Mattina, S Sheikh, A Adomeit, M Rasmussen, J. Fagerudd, N Busciantella Ricci, Nuria Vilarrasa, E Hammar, T L Thoms, L Aydın, Ron G. Rosenfeld, A Nikolajuk, R Gos, C L Morgan, H L Yu, D Dheelchand, S Ramrath, N Boudriga, Jerome I. Rotter, C Jahannault, W M Weston, Folke Lindgärde, M Hertlova, D Knight, A Monroy-Mayorga, E Pardini, A Chamson-Reig, B Franke, Janie McCluskey, Joseph Bryan, C Nikolopoulou, Christie M. Ballantyne, Fausto Santeusanio, L Pegoraro, M Lee, A Klimenko, S Jaiveer, K. Pettersson-Fernholm, Michael A. Nauck, A Ekbom-Schnell, G Deferrari, Riccardo Schiaffini, S. Pampanelli, Khan Aka., David Hopkins, Maija Wessman, M Kamarinos, Noh J-H., O Ebisui, K McCarroll, Jeppe Sturis, Peter Nowotny, N Gorbenko, Åke Sjöholm, David G. Maggs, A E Halseth, B Cresci, A A Ortiz-Gress, A Korakovouni, O Matejkova, C E Mogensen, C J Lin, Ramon Gomis, H Seaman, C Granier, Yang C-H., F Assah, O Sanchez, Fausto Machicao, Peter G. Morris, Alberto Ortiz, A Giardinelli, D Bracaglia, A Gonzalo, S Pavlatos, Andreas Lechner, F Canovic, L Sjolind, Allan Vaag, Birgitte Bruun Nielsen, David A. Ziegler, Vito Lampasona, R Gershoni-Baruch, A. Dei Cas, H Renz, E Mena, Matthew Waltham, Kim D-M., H Levanen, D D Mick, Valentina Alexandrovna Peterkova, E Meskhishvili, Sarah Nutland, R Bustani, John R. Lindsay, M Christoforidou, A Abicht, E Harno, K Cyganek, A Fitchet, S Neelotpol, P Nikishin, P Serradas, J Hinrichsen, M Halvorson, M Chovatia, B Voet, Jinny Willis, E Parretti, M Haslbeck, M Wellard, L Teng, Julio Wainstein, J S Fischer, K. Lalic, D Roggenland, I Gich, R Anwar, Maurizio Cassader, D Serota, X J Li, R J Schotzinger, Vilmundur Gudnason, Björn Zethelius, S A Wootton, W Andrzejewski, R Rezsohazy, R Gao, T Klimentova, T Mazurek, I Bruckner, C Dohrmann, R E James, G daSilva Xavier, Kim S-Y., A Dorca, Stuart J. Pocock, Terri J. Allen, I Giovos, P B Parab, N H Andersen, P Fotinakis, Miriam Cnop, H Lee, Norbert Tennagels, Omorodola I. Abatan, F Ailett, I. Lager, D Manzella, H Hut, Larry A. Distiller, G Lip, Lim S-K., Rong Zhang, T Tsuno, Steen Knudsen, M. Bajardi, Manuel Benito, Dai Sugimoto, Melvin J. Prince, D W Dunstan, D Rankins, K A Majali, G Ozansoy, Isabella Russo, S Uçak, G Annuzzi, R Talar-Wojnarowska, K Lange, S Neugebauer-Baba, Campbell H. Thompson, Eric Renard, P. D. Mountjoy, Z Morrison, Elizabeth A. Davis, Franco Cavallo, C Corvaja, R Antuña, Craig John Currie, H Linnebjerg, He Y-L., A J Palmer, Mariola R. Chacón, H Malinska, M. Jones, R Lichnovská, K Mandes, Paolo Tessari, T Mokhort, A Laina, H. L. Y. Chan, I Schmidt, R Banks, Richard G. IJzerman, L Ksinantova, G Setti, H Vaudry, A Gallo, V Spallone, Chen J-W., Thomas Danne, A Chong, M Hallschmid, S Aczel, S Hulme, N Islam, M Hosoi, P M Ternan, P Di Bartolo, N Bishara, T Shibasaki, Martin A. Osterhoff, Im S-S., M Jecht, T Hamaguchi, S Mattera, K Ways, Elizabeth Northam, U Rajala, Reinhard W. Holl, L Yang, S Panaiotopoulos, K Horvath, R Kluge, Thora B. Bodvarsdottir, Y Dong, Irene Alemanno, C McDougall, Reimar W. Thomsen, M Campbell, W Rabl, John Öhrvik, Yuichiro Yamada, Paola Ungaro, W Benzer, Mike Sampson, Roberto Trevisan, R G Radu, Aas A-M., P E Lobo, Ricardo Scott, S M Son, Josephine M. Forbes, T A Hillier, K L Wyne, Louis L. Nguyen, J Farmer, M H Tan, Kwon H-S., J Yang, L Sandvik, Franco Folli, A K Jenum, M Nguyen, W Pratipanawatr, A L Frederiksen, Rebecca Smith, Lee H-J., A Schäfer, C Manuelli, G S Denver, T Vukovich, B Maceira, K Matsumoto, K. Chokkalingam, Nurcan Üçeyler, P Modi, Timothy M. Morgan, S Mertens, B M Singh, Michaela Riedl, K Iso, C Cucurullo, G. F. Bottazzo, M Calvani, K Hur, J Wetzels, Kazuhiro Takahashi, Y Aso, H Stammer, M G Masding, Fitsum Guebre-Egziabher, J L González-Sánchez, L Armstrong, Alberto Maran, Peter G.F. Swift, S S Popovic, J Starczynski, E Vitacolonna, Luigi Laviola, R W Gelling, Marina Cardellini, D Barilla, Rosa de Diego Martínez, W H Landschulz, Anne Mette Rosenfalck, R K Wong, Kevin E. Schneider, K Peros, Giuseppe Nanni, F Zhang, I Rákóczi, T Iburi, M Nakhjavani, X Q Zhang, S Tournis, Per Lav Madsen, Graham A. Hitman, A. Tura, K Laubner, N D Kostic, Lawrence M. Dolan, R. Sinha Roy, J A Wagner, J. Tuomilehto, J Hauptman, M Abdel-Ghany, D Lacombe, Toralph Ruge, Johannes A Maassen, Triantafyllos Didangelos, K Sasaki, I Argüelles, Klaus Levin, C Popow, Emanuel Christ, R Chetty, L Baillet-Blanco, Jo-Ann Salmon, T Mine, James L. Trevaskis, I Franke, J Gorski, E A Andrianova, A Dayan, A Caballero, Aleksandra Gilis-Januszewska, M Yasujima, Z Kasalová, C.D.A. Stehouwer, F. K. Gorus, G A Nichols, A Glowania, David P. Strachan, P Fredlund, N. F. da Silva, P Reboldi, M Sausbier, K H Groenier, G Stuccio, N Guttman, K R Ahmed, A D Ristic, T Kapellen, J Coutcher, Aldo V. Greco, Oswald Wagner, A Zagayko, Maria Alevizaki, B B Zhang, W F Ferris, Jenny Fredriksson, Lois Jovanovic, J Hänninen, R De Giglio, Kazuo Yagui, O Potterat, P Hamliton, R E Scranton, B Mankovsky, A Stylianou, B Fellström, Abdel-Wahab Yha., M Kitagawa, Katherine L. Baldock, F R Johnson, F Baigts, S D'Addato, F J Sanz, A Mistry, S D Wise, T Pratipanawatr, U R Fölsch, James R.C. Parkinson, Claudia Sommer, C Park, F E Griffiths, M L Martí, R Demirtunc, S Taniguchi, J Lundkvist, T Siegmund, Juan Sztajzel, C Dienesch, F Baumgartner, L Scalone, T M Mckolanis, K Otake, Ullrik Pedersen-Bjergaard, T M Vriesendorp, Michael B. Wheeler, Henry Schmitt, Peter Hovind, S Lange, Stephane Roze, L. Van Gaal, B Klaproth, Anthony E. Civitarese, D Eckland, A Dagar, D F Hopkins, Kari Stefansson, C Gonzalez-Yanes, B Meyboom-de Jong, D. J. Betteridge, K Buhling, M Crepaldi, Ana M. Wägner, L Renna, L Volpe, R McBride, V Corbo, E O Brennesvik, R P Hayes, R Abdollahnia, G Viviani, C F Liew, Francisco Pérez-Bravo, Jeffrey Baron, Brian M. Frier, H H Samira, D Szentendrei, K. J. Schjoedt, W K Waldhäusl, D Gniuli, D Zou, G Tschank, V Urbančič, A L Nolan, Albertini J-P., J Malcomson, M Larbig, C Cheyssac, K Aurich, C M Kesson, S Heller, Maija E. Miettinen, R F Luco, Adrian J. Cameron, Luigi Mattiello, Z. Metelko, X E Zhang, M Parramón, I. G. 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Jensen, A D'Avanzo, J Monaghan, K P Yeo, Guivarch P-H., B Bauduceau, D Weghuber, P Tatti, J Ybarra, S Gwozdziewiczová, E Gasparini, B Saltin, Charlotte Granhall, Howard Leventhal, R Marin, M Tumiati, Cicero Afg., L Csémy, B Berger, S Mikros, D Dall'Asta, M Shahmanesh, Y G Vasiljev, F Potthoff, H S Randeva, G De Berardis, J O Logan, K Warncke, P Uitterlinden, E Rehring, K Gilmore, K Shankhdhar, V V Bojko, M Vahatalo, E A Korolyova, D Wiemann, P G Lankisch, D Hendrie, F Galtier, M Rybarczyk, Gisela Dahlquist, N N Rudovich, G Stein, A Liebl, F Tan, A Westerlund, S Gronemann, I Franklin, Jonathan A. Prince, Peter Arner, E Skliros, T. Sparre, M Vigas, Maddalena Trombetta, L. Bjerre Knudsen, A C Sima, I Dubroca, Alastair Gray, I Weets, R Ferraresi, Schauer Ujw., E. Leinonen, S Corazza, Jonathan Levy, P K Prakash, R Guzder, S. Barnhill, John Blangero, J Herreros, G. de Vries, Cheng Ptw., A Macías-Batista, K. 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Hansen, T Watanabe, Gang Hu, Malik Rja., T Kennedy-Martin, Ulla M Smidt, J.M. Dekker, A A Fisher, H Liu, R E Pratley, B Sun, C Fledelius, J F Raposo, R Langham, Ahn S-Y., B R Waterhouse, Shaoping Deng, W Ricart, S V Melnichenko, Henrike Sell, M. Tomalino, N Takeda, Paola Massucco, A Harlan, W Henrich, C D Byrne, R Junik, Khalid Hussain, D Pop Gorceva, Torben Hansen, C Ritterath, K Ogawa, D V Phan, Bradley S Metcalf, Robb E. Moses, Juan P. Frias, Hitoshi Ishii, C Brisard, P Wolkow, H H Maurer, Ingo Rustenbeck, Juris J. Meier, Octavian Savu, S D Lin, V B Bregovski, A Fox, S Cicala, M. Koenen, L Vignati, O de Divitiis, Constantin Ionescu-Tirgoviste, Kilian Rittig, J Song, Riccardo Candido, F Cohen-Boulakia, U Shankhdhar, P Jahan, Antonio Tiengo, E Liepinsh, C Álvarez, Sigurd Lenzen, James E. 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Chauveau, P, Combe, C, Baillet blanco, L, Beauvieux, M, Gin, H, Heinrich, S, Steiner, T, Ott, U, Holdass, H, Fellström, B, Jardine, A, Staffler, B, Logan, J, Gimpelewicz, C, Stanciu, C, Pena, C, Serafinceanu, C, González posada, J, Hernández, D, Pérez tamajó, L, Ló, A, Herná Alarcó, M, Meneses, M, Barsotti, M, Rizzo, G, Schmauss, S, Havrdova, T, Saudek, F, Boucek, P, Adamec, M, Invitti, C, Gilardini, L, Parati, G, Mazzilli, G, Pontiggia, B, Sartorio, A, Lutgers, H, Groenier, K, Zasadzinska, G, Saryusz wolska, M, Kurktschiev, D, Majdrakova, I, Varbanova, T, Todorova, B, Bajo martinez, A, Bernal, E, Sanchez, O, Ugalde canitrot, A, Sanchez largo, E, Coca robinot, D, Fabregate, R, Calbacho, M, Marquez, J, Saban ruiz, J, Penesova, A, Cizmarova, E, Blazicek, P, De Jongh, R, Serné, E, Ijzerman, R, De Vries, G, Andersen, N, Knudsen, S, Helleberg, K, Mogensen, C, Waluś, M, Idzior waluś, B, Sztefko, K, Cieślik, G, Fedak, D, Wozniakiewicz, E, Lin, S, Guo, M, Lin, C, Liu, X, Francisco, M, Rodriguez rosas, H, Peiró martinez, I, Macías batista, A, Harte, A, Rodriguez cuenca, S, Valsamakis, G, Chetty, R, Anderson, L, Roca, P, Matyka, K, Lasalle, J, Hershon, K, Berman, L, Gibson, E, Gillen, D, Maroni, J, Simmons, D, Hiukka, A, Forder, P, Leinonen, E, Hilden, H, Fruchart, J, Keech, A, Farnier, M, Freeman, M, Macdonell, G, Perevozskaya, I, Mitchel, Y, Gumbiner, B, Didangelos, T, Athyros, V, Mikhailidis, D, Papageorgiou, A, Bouloukos, V, Pehlivanidis, A, Symeonidis, A, Elisaf, M, Mckenney, J, Insull, W, Lewin, A, Maccubbin, D, Kush, D, Schuster, H, Barter, P, Stender, S, Bonnet, J, Morrell, J, Watkins, C, Kallend, D, Stalenhoef, A, Ballantyne, C, Murin, J, Tonstad, S, Rose, H, Wilpshaar, W, Jenkins, A, Karschimkus, C, Dragicevic, G, Rowley, K, Wolthers, T, Best, J, Voet, B, Murdoch, S, Marcovina, S, Brunzell, J, Caparevic, Z, Kostic, N, Ilic, S, Sartore, G, Piarulli, F, Cantaro, S, Reitano, R, Fiore, C, Marin, R, Bassan, S, Manzato, E, Fedele, D, Solini, A, Santini, E, Thornalley, P, Babaei jadidi, R, Karachalias, N, Kupich, C, Ahmed, N, Fowler, A, Baker, A, Starczynski, J, O'Hare, P, Szepietowska, B, Szelachowska, M, Puch, U, Glebocka, A, Quinn, D, Mcternan, C, Bonser, R, Idzior walus, B, Woźniakiewicz, E, Dimitriou, K, Apostolou, O, Kontela, E, Devangelio, E, Gould, E, Serri, O, Roussin, A, Buithieu, J, Mamputu, J, Renier, G, Giordanetti, S, De Amici, E, Poggi, G, Turpini, C, Fratino, P, Garzaniti, A, Banu, I, Paries, J, Roman, G, Negrean, M, Bala, C, Nita, C, Kistorp, C, Gustafsson, F, Chong, A, Lip, G, Galatius, S, Ari, N, Sahilli, M, Ceylan isık, A, Ozansoy, G, Karasu yilmaz, C, Matteucci, E, Rosada, J, Pallini, M, Evangelista, I, Cassetti, G, Giusti, C, Giampietro, O, Capaldo, B, Galderisi, M, Cicala, S, Turco, A, Imbroinise, A, Nosso, G, D'Errico, A, De Divitiis, O, Klimontov, V, Korolyova, E, Jeltova, L, Bondar, I, Tarkun, I, Arslan, B, Canturk, Z, Tarkun, P, Agacdiken, A, Komsuoglu, B, Méneveau, N, Pierre justin, E, Alsayed, M, Sabbah, R, Paulin, S, Marcu, S, Tauveron, I, Zimmermann, C, Schiele, F, Seronde, M, Vautrin, P, Lusson, J, Thieblot, P, Bernard, Y, Mistry, A, Pye, M, Peovska, I, Maksimovic Pavlovic, J, Vavlukis, M, Pop Gorceva, D, Bosevski, M, Scognamiglio, R, Negut, C, De Kreutzenberg, S, Madonna, R, De Caterina, R, Willerson, J, Geng, Y, Vahsen, S, Ledwig, D, Ramrath, S, Frantz, S, Schmidt, I, Calvillo, L, Dienesch, C, Elbing, I, Bischoff, H, Ertl, G, Bauersachs, J, Davydov, A, Mkrtum'Yan, A, Baranova, L, Ikeda, Y, Suehiro, T, Osaki, F, Ota, K, Arii, K, Kumon, Y, Hashimoto, K, Doney, A, Morris, A, Palmer, C, Byun, S, Doo, H, Pagnin, E, Calo, L, Fadini, G, Kubaszek, A, Chai, S, Chai, Q, Rasmussen, L, Ledet, T, Wogensen, L, Lengyel, C, Varró, A, Virág, L, Magyar, J, Bíró, T, Jost, N, Skoumal, R, Nánási, P, Tóth, M, Horkay, F, Papp, J, Zacharopoulou, O, Athanaselis, S, Tsokos, N, Doupis, J, Psallas, M, Cokkinos, D, Pavlatos, S, Liatis, S, Akhobadze, T, Dzneladze, L, Samarguliani, I, Taskiran, M, Rasmussen, V, Jensen, G, Fisher, A, Petrovsky, N, Srikusalanukul, W, Budge, M, Trifunovic zamaklar, D, Zivkovic, M, Jelic, V, Vukomanovic, G, Ristic, A, Seferovic, P, Costa, J, Duarte, S, Manley, S, Sailesh, S, Venkataraman, A, Haider, Y, Groza, I, Oprean, M, Ardelean, A, Morosanu, A, Darkow, T, Vanderplas, A, Mamas, M, Mcelduff, P, Burns, J, Edwards, R, Fitchet, A, Young, R, Gibson, J, Lichiardopol, R, Niculescu, N, Totora, A, Pencea, C, Tomescu, I, Cinteza, M, Manicardi, V, Coscelli, C, Navazio, A, Catellani, E, Michelini, M, Dall'Asta, D, Guberti, A, Piazza, A, Gasparini, E, Pantaleoni, M, Guiducci, U, Manari, A, Sejil, S, Janand delenne, B, Avierinos, J, Habib, G, Labastie, N, Vague, P, Lassmann vague, V, Luźniak, P, Tatoń, J, Wojciechowska Luźniak, A, Zairis, M, Lyras, A, Patsourakos, N, Tsirimbis, V, Foussas, S, Lupón, J, Urrutia, A, Herreros, J, González, B, Coll, R, Altimir, S, Prats, M, Valle, V, Abreu padí, C, Rábago, G, Ivanova, L, Brasacchio, D, Harno, E, Keenan, A, Li, H, Lu, Z, Ke, L, Liu, H, Jeong, I, Chae, M, Choi, M, Yoo, H, Kim, C, Yun, M, Na, M, Kang, Y, Kong, O, Son, S, Kim, I, Tanaka, N, Hosoi, M, Matsuyama, Y, Fukumoto, M, Yamakita, T, Yoshioka, K, Ishii, T, Sato, T, Fujii, S, Aoki, T, Shibata, T, Mizutani, N, Suzuki, J, Fowelin, J, Samuelsson, P, Brandrup wogsen, G, Okumura, K, Tokmakova, A, Staroverova, D, Antcieferov, M, Shutichina, I, Kuntchevich, G, Vriesendorp, T, Morélis, Q, Legemate, D, Schaper, F, Mainas, E, Gkioulmpasanis, I, Panagiotou, I, Vassilikos, G, Skorda, L, Sidira, M, Christoforidou, M, Alaveras, A, Artikis, V, Evdemon, E, Lechleitner, M, Koch, T, Ebenbichler, C, Sturm, W, Moretti, L, Moruzzo, D, Boldrini, E, Pandolfo, C, Kameyama, M, Iwasa, R, Cho, M, Nam, J, Huh, K, Kaplar, M, Paragh, G, Erdei, A, Csongradi, E, Garai, I, Varga, J, Galuska, L, Udvardy, M, Higa, M, Kaneko, Y, Hiroi, N, Koziarska, D, Nowacki, P, Majkowska, L, Luzniak, P, Wojciechowska luźniak, A, Tushuizen, M, Nieuwland, R, Snoeck, D, Sturk, A, Diamant, M, Aguiar, L, Bahia, L, Villela, N, Laflor, C, Conde, C, Bottino, D, Dorigo, D, Bouskela, E, Pu, S, Luo, Z, Lam, K, Dan, Q, Xu, A, Shen, J, Cheng, K, Xu, J, Thamer, C, Stefan, N, Haap, M, Heller, E, Tschritter, O, De Prado, A, Ortiz, A, Ybarra, J, Gich, I, Pou, J, Ehren, M, Roggenland, D, Reinsen, B, Klein, H, Rittig, K, Stock, J, Kocher, B, Balletshofer, B, Shon, H, Chung, D, Nakatani, Y, Matsuhisa, M, Kaneto, H, Hatazaki, M, Yoshiuchi, K, Katakami, N, Kawamori, D, Ohtoshi, K, Sakamoto, K, Matsuoka, T, Ozawa, K, Ogawa, S, Hori, M, Yamasaki, Y, Zitouni, K, Harry, D, Nourooz zadeh, J, Earle, K, Olesen, P, Franco, L, Corvaja, C, Semplicini, A, Ceylan işık, A, Arı, N, Rösen, P, Lee, I, Park, K, Jung, E, Shin, D, Jo, S, Obuobie, K, Prakash, P, Hanna, F, Lazarus, J, Varadhan, L, Gurushankar, J, James, D, Sheikh, S, Gaede, P, Zou, D, Vilarrasa, N, Perez maraver, M, Mena, E, Perez, D, Setti, G, Buckingham, R, Urbančič, V, Stefanovska, A, Bernjak, A, Ažman juvan, K, Kocijančič, A, Glowania, A, Filters, T, Fosmark, D, Torjesen, P, Kilhovd, B, Berg, T, Sandvik, L, Hanssen, K, Mentink, C, Donchenko, G, Stepanenko, S, Maingrette, F, Deng, H, Lindenmair, A, Freudenthaler, A, Baumgartner parzer, S, Nizheradze, K, Khoruzhenko, A, Tronko, N, Sheu, W, Ou, H, Shen, H, Lin, T, Wu, H, Yang, C, Mogylnytska, L, Schmoelzer, I, Davies, J, Band, M, Struthers, A, Prázný, M, Škrha, J, Kasalová, Z, Neelotpol, S, Jahan, P, Kauschke, S, Harrop, C, Schäfer, A, Widder, J, Eigenthaler, M, Walter, U, Uchimura, I, Ikebukuro, M, Kaibara, M, Hirata, M, Helal, R, Pervin, F, Yang, X, Jansson, P, Nagaev, I, Jack, M, Carvalho, E, Sunnerhagen, K, Cam, M, Cushman, S, Smith, U, Creely, S, Farmer, J, Gustafson, B, Kusminski, C, Krusinova, E, Wohl, P, Klementova, M, Lanska, V, Mcdougall, C, Kelly, I, Abbas, Z, Lutale, J, Archibald, L, Karunajeewa, H, Stingemore, N, Stuccio, G, Mcgechie, D, Muller, L, Hak, E, Goudzwaard, W, Montorsi, F, Homering, M, Sprenger, K, Goldstein, I, Asnaghi, V, Ferrari, G, Rastaldi, M, Gabellini, D, Dell'Antonio, G, Maestroni, A, Ruggieri, D, Luzi, L, Piemonti, L, Zerbini, G, Anafaroglu, I, Tutuncu, N, Sultana, M, Siddiqua, N, Iwasaki, T, Nakajima, A, Yoneda, M, Mukasa, K, Tanaka, S, and Sekihara, H
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0303 health sciences ,medicine.medical_specialty ,business.industry ,EASD ,Endocrinology, Diabetes and Metabolism ,Human physiology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Family medicine ,Internal Medicine ,Medicine ,business ,030217 neurology & neurosurgery ,030304 developmental biology - Published
- 2004
16. Subacute Thyroiditis Complicating COVID-19 Infection.
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Henke K, Odermatt J, Ziaka M, and Rudovich N
- Abstract
Subacute thyroiditis (SAT) is a self-limited inflammatory disease and a rare cause of thyrotoxicosis. Although the exact etiology of SAT is not sufficiently understood, it is generally associated to viral infections. Current evidence highlights that SAT may be a potentially uncommon manifestation of ongoing Coronavirus disease 2019 (COVID-19) infection or a post-viral complication of the disease. Despite that SAT is a rare manifestation associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease both in ongoing and resolved COVID-19 infection, the ever-increasing numbers of COVID-19 patients strengthens the possibility that this particular disease entity will be of more immediate concern in the future. The current work aims to summarize the approach of SARS-CoV-2-associated SAT, present its pathophysiology, outline current research evidence found in the literature, and discuss potential differential diagnoses and diagnostic dilemmas through an illustrative case., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)
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- 2023
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17. Physical Performance and Non-Esterified Fatty Acids in Men and Women after Transcatheter Aortic Valve Implantation (TAVI).
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Härdrich M, Haase-Fielitz A, Fielitz J, Boschmann M, Pivovarova-Ramich O, Pfeiffer AFH, Rudovich N, Weylandt KH, and Butter C
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- Aged, Aged, 80 and over, Aortic Valve Stenosis surgery, Bicycling, Body Mass Index, Female, Humans, Male, Prospective Studies, Reference Values, Risk Factors, Sex Factors, Treatment Outcome, Walking, Biomarkers blood, Fatty Acids, Nonesterified blood, Physical Functional Performance, Transcatheter Aortic Valve Replacement
- Abstract
Background: Men and women with valvular heart disease have different risk profiles for clinical endpoints. Non-esterified fatty acids (NEFA) are possibly involved in cardio-metabolic disease. However, it is unclear whether NEFA concentrations are associated with physical performance in patients undergoing transcatheter aortic valve implantation (TAVI) and whether there are sex-specific effects., Methods: To test the hypothesis that NEFA concentration is associated with sex-specific physical performance, we prospectively analysed data from one hundred adult patients undergoing TAVI. NEFA concentrations, physical performance and anthropometric parameters were measured before and 6 and 12 months after TAVI. Physical performance was determined by a six-minute walking test (6-MWT) and self-reported weekly bicycle riding time., Results: Before TAVI, NEFA concentrations were higher in patients (44 women, 56 men) compared to the normal population. Median NEFA concentrations at 6 and 12 months after TAVI were within the reference range reported in the normal population in men but not women. Men but not women presented with an increased performance in the 6-MWT over time ( p = 0.026, p = 0.142, respectively). Additionally, men showed an increased ability to ride a bicycle after TAVI compared to before TAVI ( p = 0.034). NEFA concentrations before TAVI correlated with the 6-MWT before TAVI in women (Spearman's rho -0.552; p = 0.001) but not in men (Spearman's rho -0.007; p = 0.964). No association was found between NEFA concentrations and physical performance 6 and 12 months after TAVI., Conclusions: NEFA concentrations improved into the reference range in men but not women after TAVI. Men but not women have an increased physical performance after TAVI. No association between NEFA and physical performance was observed in men and women after TAVI.
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- 2022
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18. Insulin Directly Regulates the Circadian Clock in Adipose Tissue.
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Tuvia N, Pivovarova-Ramich O, Murahovschi V, Lück S, Grudziecki A, Ost AC, Kruse M, Nikiforova VJ, Osterhoff M, Gottmann P, Gögebakan Ö, Sticht C, Gretz N, Schupp M, Schürmann A, Rudovich N, Pfeiffer AFH, and Kramer A
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- 3T3-L1 Cells, Adipocytes drug effects, Adipocytes metabolism, Adipose Tissue metabolism, Animals, Humans, Mesenchymal Stem Cells drug effects, Mice, Nuclear Receptor Subfamily 1, Group D, Member 1 genetics, Nuclear Receptor Subfamily 1, Group D, Member 1 metabolism, Period Circadian Proteins genetics, Period Circadian Proteins metabolism, Promoter Regions, Genetic drug effects, Adipose Tissue drug effects, Circadian Clocks drug effects, Circadian Rhythm drug effects, Insulin pharmacology
- Abstract
Adipose tissue (AT) is a key metabolic organ which functions are rhythmically regulated by an endogenous circadian clock. Feeding is a "zeitgeber" aligning the clock in AT with the external time, but mechanisms of this regulation remain largely unclear. We tested the hypothesis that postprandial changes of the hormone insulin directly entrain circadian clocks in AT and investigated a transcriptional-dependent mechanism of this regulation. We analyzed gene expression in subcutaneous AT (SAT) of obese subjects collected before and after the hyperinsulinemic-euglycemic clamp or control saline infusion (SC). The expressions of core clock genes PER2, PER3 , and NR1D1 in SAT were differentially changed upon insulin and saline infusion, suggesting insulin-dependent clock regulation. In human stem cell-derived adipocytes, mouse 3T3-L1 cells, and AT explants from mPer2
Luc knockin mice, insulin induced a transient increase of the Per2 mRNA and protein expression, leading to the phase shift of circadian oscillations, with similar effects for Per1 Insulin effects were dependent on the region between -64 and -43 in the Per2 promoter but not on CRE and E-box elements. Our results demonstrate that insulin directly regulates circadian clocks in AT and isolated adipocytes, thus representing a primary mechanism of feeding-induced AT clock entrainment., (© 2021 by the American Diabetes Association.)- Published
- 2021
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19. Hepatic Wnt1 Inducible Signaling Pathway Protein 1 (WISP-1/CCN4) Associates with Markers of Liver Fibrosis in Severe Obesity.
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Pivovarova-Ramich O, Loske J, Hornemann S, Markova M, Seebeck N, Rosenthal A, Klauschen F, Castro JP, Buschow R, Grune T, Lange V, Rudovich N, and Ouwens DM
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- Adult, CCN Intercellular Signaling Proteins genetics, CD11 Antigens genetics, CD11 Antigens metabolism, Cell Line, Chemokine CCL2 genetics, Chemokine CCL2 metabolism, Collagen genetics, Collagen metabolism, Female, Humans, Liver pathology, Liver Cirrhosis etiology, Male, Matrix Metalloproteinase 9 genetics, Matrix Metalloproteinase 9 metabolism, Middle Aged, Obesity, Morbid complications, Proto-Oncogene Proteins genetics, Tissue Inhibitor of Metalloproteinase-1 genetics, Tissue Inhibitor of Metalloproteinase-1 metabolism, Transforming Growth Factor beta genetics, Transforming Growth Factor beta metabolism, CCN Intercellular Signaling Proteins metabolism, Liver metabolism, Liver Cirrhosis metabolism, Obesity, Morbid metabolism, Proto-Oncogene Proteins metabolism
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Liver fibrosis is a critical complication of obesity-induced fatty liver disease. Wnt1 inducible signaling pathway protein 1 (WISP1/CCN4), a novel adipokine associated with visceral obesity and insulin resistance, also contributes to lung and kidney fibrosis. The aim of the present study was to investigate the role of CCN4 in liver fibrosis in severe obesity. For this, human liver biopsies were collected from 35 severely obese humans (BMI 42.5 ± 0.7 kg/m
2 , age 46.7 ± 1.8 y, 25.7% males) during bariatric surgery and examined for the expression of CCN4, fibrosis, and inflammation markers. Hepatic stellate LX-2 cells were treated with human recombinant CCN4 alone or in combination with LPS or transforming growth factor beta (TGF-β) and examined for fibrosis and inflammation markers. CCN4 mRNA expression in the liver positively correlated with BMI and expression of fibrosis markers COL1A1, COL3A1, COL6A1, αSMA, TGFB1, extracellular matrix turnover enzymes TIMP1 and MMP9, and the inflammatory marker ITGAX/CD11c. In LX-2 cells, the exposure to recombinant CCN4 caused dose-dependent induction of MMP9 and MCP1. CCN4 potentiated the TGF-β-mediated induction of COL3A1, TIMP1, and MCP1 but showed no interaction with LPS treatment. Our results suggest a potential contribution of CCN4 to the early pathogenesis of obesity-associated liver fibrosis.- Published
- 2021
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20. Shotgun Lipidomics Discovered Diurnal Regulation of Lipid Metabolism Linked to Insulin Sensitivity in Nondiabetic Men.
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Kessler K, Gerl MJ, Hornemann S, Damm M, Klose C, Petzke KJ, Kemper M, Weber D, Rudovich N, Grune T, Simons K, Kramer A, Pfeiffer AFH, and Pivovarova-Ramich O
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- Adult, Blood Glucose metabolism, Carbohydrate Metabolism drug effects, Carbohydrate Metabolism physiology, Circadian Rhythm drug effects, Cross-Over Studies, Diet, High-Fat, Dietary Carbohydrates administration & dosage, Dietary Carbohydrates metabolism, Dietary Carbohydrates pharmacology, Dietary Fats administration & dosage, Dietary Fats metabolism, Dietary Fats pharmacology, Germany, Humans, Insulin blood, Lipid Metabolism drug effects, Lipidomics methods, Male, Meals, Middle Aged, Postprandial Period drug effects, Circadian Rhythm physiology, Insulin Resistance physiology, Lipid Metabolism physiology
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Context: Meal timing affects metabolic homeostasis and body weight, but how composition and timing of meals affect plasma lipidomics in humans is not well studied., Objective: We used high throughput shotgun plasma lipidomics to investigate effects of timing of carbohydrate and fat intake on lipid metabolism and its relation to glycemic control., Design: 29 nondiabetic men consumed (1) a high-carb test meal (MTT-HC) at 09.00 and a high-fat meal (MTT-HF) at 15.40; or (2) MTT-HF at 09.00 and MTT-HC at 15.40. Blood was sampled before and 180 minutes after completion of each MTT. Subcutaneous adipose tissue (SAT) was collected after overnight fast and both MTTs. Prior to each investigation day, participants consumed a 4-week isocaloric diet of the same composition: (1) high-carb meals until 13.30 and high-fat meals between 16.30 and 22:00 or (2) the inverse order., Results: 12 hour daily lipid patterns showed a complex regulation by both the time of day (67.8%) and meal composition (55.4%). A third of lipids showed a diurnal variation in postprandial responses to the same meal with mostly higher responses in the morning than in the afternoon. Triacylglycerols containing shorter and more saturated fatty acids were enriched in the morning. SAT transcripts involved in fatty acid synthesis and desaturation showed no diurnal variation. Diurnal changes of 7 lipid classes were negatively associated with insulin sensitivity, but not with glucose and insulin response or insulin secretion., Conclusions: This study identified postprandial plasma lipid profiles as being strongly affected by meal timing and associated with insulin sensitivity., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2020
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21. Circulating Wnt1-inducible signaling pathway protein-1 (WISP-1/CCN4) is a novel biomarker of adiposity in subjects with type 2 diabetes.
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Klimontov VV, Bulumbaeva DM, Fazullina ON, Lykov AP, Bgatova NP, Orlov NB, Konenkov VI, Pfeiffer AFH, Pivovarova-Ramich O, and Rudovich N
- Abstract
Background: Wnt1-inducible signaling pathway protein 1, or cellular communication network factor 4 (CCN4), a member of CCN family of secreted, extracellular matrix associated signaling proteins, recently was validated as a novel adipose tissue derived cytokine., Objective: To assess the relationships between circulating CCN4, adipose tissue distribution and function, and chronic low-grade inflammation in subjects with type 2 diabetes., Methods: We observed 156 patients with type 2 diabetes and 24 healthy controls. Serum levels of CCN4, hsCRP and alpha1-acid glycoprotein (alpha1-AGP) were measured by ELISA. Serum concentrations of leptin, resistin, visfatin, adipsin, adiponectin, IL-6, IL-8, IL-18 and TNF-alpha were determined by multiplex analysis. Fat mass and distribution was assessed by DEXA. Mean diameter of adipocytes was estimated in samples of subcutaneous adipose tissue., Results: Patients with diabetes had higher levels of circulating CCN4, leptin, resistin, adipsin, visfatin, hsCRP, alpha1-AGP, and IL-6 (all p < 0.02). The CCN4 concentration correlated positively with percentage of fat mass in central abdominal area, as well as with leptin, resistin and visfatin levels; negative correlation was found between CCN4 and mean adipocyte diameter. In multiple regression analysis fat mass in central abdominal area was independent predictor for CCN4 concentration., Conclusion: In subjects with type 2 diabetes serum levels of CCN4 are associated with central abdominal fat mass and adipose tissue dysfunction.
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- 2020
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22. Effects of plant and animal high protein diets on immune-inflammatory biomarkers: A 6-week intervention trial.
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Markova M, Koelman L, Hornemann S, Pivovarova O, Sucher S, Machann J, Rudovich N, Thomann R, Schneeweiss R, Rohn S, Pfeiffer AFH, and Aleksandrova K
- Subjects
- Adipokines blood, Aged, Biomarkers blood, Diet, High-Protein methods, Female, Humans, Leukocyte L1 Antigen Complex blood, Male, Middle Aged, Transforming Growth Factor beta blood, Animal Proteins, Dietary blood, Animal Proteins, Dietary immunology, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 immunology, Inflammation blood, Plant Proteins, Dietary blood, Plant Proteins, Dietary immunology
- Abstract
Background & Aims: Pro-inflammatory biomarkers are well-established contributors to insulin resistance and represent valid targets for diabetes management and prevention. Yet, little is known whether nutrition could play a role in modulating various aspects of immune-inflammatory responses. Our aim is to assess the effect of isocaloric animal and plant protein dietary interventions on selected biomarkers representing various immune-inflammatory pathways., Methods: We enrolled 37 participants with type 2 diabetes (age 64 ± 6 years, body mass index 30.2 ± 3.6 kg/m
2 , glycated hemoglobin 7.0 ± 0.6%) who underwent an either high-animal protein (AP) or high-plant protein (PP) diet (30 E% protein, 40 E% carbohydrates, 30 E% fat) for 6-weeks. Clinical examinations were performed at beginning and end of the study. Levels of pro-inflammatory adipokines [chemerin, progranulin], cytokines [tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), soluble urokinase-type plasminogen activator receptor (suPAR), transforming growth factor beta 1 (TGF-β1)], and proteins [calprotectin, lactoferrin and growth differentiation factor 15 (GDF-15)] were determined in blood serum using enzyme-linked immunosorbent assay., Results: Chemerin and progranulin concentrations decreased following AP and PP diets. TGF-β1 increased in AP and decreased in PP, whereas calprotectin increased in PP and decreased in AP. No statistically significant differences in the concentrations of IL-6, TNF-α, suPAR, lactoferrin and GDF-15 could be seen in either of the protein diet arms., Conclusions: These results suggest that both AP and PP diets may effectively reduce the levels of the pro-inflammatory adipokines chemerin and progranulin. The effects on the additional immune-inflammatory biomarkers seem to be more complex., Clinical Trial Registry Number: NCT02402985 (ww.clinicaltrials.gov)., (Copyright © 2019. Published by Elsevier Ltd.)- Published
- 2020
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23. Endogenously released GIP reduces and GLP-1 increases hepatic insulin extraction.
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Keyhani-Nejad F, Barbosa Yanez RL, Kemper M, Schueler R, Pivovarova-Ramich O, Rudovich N, and Pfeiffer AFH
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- Adult, Case-Control Studies, Cross-Over Studies, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 pathology, Female, Humans, Isomaltose administration & dosage, Isomaltose analogs & derivatives, Liver drug effects, Male, Middle Aged, Sucrose administration & dosage, Diabetes Mellitus, Type 2 drug therapy, Gastric Inhibitory Polypeptide pharmacology, Glucagon-Like Peptide 1 pharmacology, Incretins pharmacology, Insulin metabolism, Insulin Resistance, Liver metabolism
- Abstract
GIP was proposed to play a key role in the development of non- alcoholic fatty liver disease (NAFLD) in response to sugar intake. Isomaltulose, is a 1,6-linked glucose-fructose dimer which improves glucose homeostasis and prevents NAFLD compared to 1,2-linked sucrose by reducing glucose-dependent insulinotropic peptide (GIP) in mice. We compared effects of sucrose vs. isomaltulose on GIP and glucagon-like peptide-1 (GLP-1) secretion, hepatic insulin clearance (HIC) and insulin sensitivity in normal (NGT), impaired glucose tolerant (IGT) and Type 2 diabetes mellitus (T2DM) participants. A randomized crossover study was performed in 15 NGT, 10 IGT and 10 T2DM subjects. In comparison to sucrose, peak glucose concentrations were reduced by 2.3, 2.1 and 2.5 mmol/l (all p < 0.05) and insulin levels were 88% (p < 0.01, NGT), 32% (p < 0.05, IGT) and 55% (T2DM) lower after the isomaltulose load. Postprandial GIP
iAUC concentrations were decreased (56%, p < 0.01 in NGT; 42%, p < 0.05 in IGT and 40%,p < 0.001 in T2DM) whereas GLP-1iAUC was 77%, 85% and 85% higher compared to sucrose (p < 0.01), respectively. This resulted in ∼35 - 50% improved insulin sensitivity and reduced insulinogenic index after isomaltulose, which correlated closely with improved HIC, respectively (r = 0.62, r=-0.70; p < 0.001). HIC was inversely related to GIP (r=-0.44, p < 0.001) and positively related to GLP-1 levels (r = 0.40, p = 0.001). CONCLUSION: Endogenously released GIP correlated with reduced, and GLP-1 with increased hepatic insulin extraction. Increased peripheral insulin levels may contribute to insulin resistance and obesity. We propose that the unfavorable effects of high glycemic index Western diets are related to increased GIP-release and reduced HIC., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)- Published
- 2020
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24. Saliva Samples as A Tool to Study the Effect of Meal Timing on Metabolic And Inflammatory Biomarkers.
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Kessler K, Hornemann S, Rudovich N, Weber D, Grune T, Kramer A, Pfeiffer AFH, and Pivovarova-Ramich O
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- Adult, Biomarkers chemistry, Biomarkers metabolism, Dietary Carbohydrates, Dietary Fats, Humans, Male, Middle Aged, Inflammation metabolism, Meals, Saliva chemistry
- Abstract
: Meal timing affects metabolic regulation in humans. Most studies use blood samples for their investigations. Saliva, although easily available and non-invasive, seems to be rarely used for chrononutritional studies. In this pilot study, we tested if saliva samples could be used to study the effect of timing of carbohydrate and fat intake on metabolic rhythms. In this cross-over trial, 29 nonobese men were randomized to two isocaloric 4-week diets: (1) carbohydrate-rich meals until 13:30 and high-fat meals between 16:30 and 22:00 or (2) the inverse order of meals. Stimulated saliva samples were collected every 4 h for 24 h at the end of each intervention, and levels of hormones and inflammatory biomarkers were assessed in saliva and blood. Cortisol, melatonin, resistin, adiponectin, interleukin-6 and MCP-1 demonstrated distinct diurnal variations, mirroring daytime reports in blood and showing significant correlations with blood levels. The rhythm patterns were similar for both diets, indicating that timing of carbohydrate and fat intake has a minimal effect on metabolic and inflammatory biomarkers in saliva. Our study revealed that saliva is a promising tool for the non-invasive assessment of metabolic rhythms in chrononutritional studies, but standardisation of sample collection is needed in out-of-lab studies., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
- Published
- 2020
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25. Effects of diets high in animal or plant protein on oxidative stress in individuals with type 2 diabetes: A randomized clinical trial.
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Pivovarova-Ramich O, Markova M, Weber D, Sucher S, Hornemann S, Rudovich N, Raila J, Sunaga-Franze D, Sauer S, Rohn S, Pfeiffer AFH, and Grune T
- Subjects
- Aged, Humans, Middle Aged, Animal Proteins, Dietary, Antioxidants, Oxidative Stress, Plant Proteins, Dietary, Diabetes Mellitus, Type 2 diet therapy, Diabetes Mellitus, Type 2 metabolism
- Abstract
High-protein diet is a promising strategy for diabetes treatment supporting body weight control, improving glycaemic status, cardiovascular risk factors and reducing liver fat. Here, we investigated effects of diets high in animal (AP) or plant (PP) protein on oxidative stress and antioxidant status in individuals with type 2 diabetes (T2DM). 37 obese individuals (age 64.3 ± 1.0 years) with T2DM were randomized to an isocaloric diet (30 energy(E)% protein, 30 E% fat and 40 E% carbohydrates) rich in AP or PP for 6 weeks. Markers of oxidative and nitrosative stress and antioxidant status in plasma and nitrate/nitrite levels in urine were assessed. Gene expression in subcutaneous adipose tissue (SAT) was analysed by RNA-Seq and real-time PCR. Both AP and PP diets similarly reduced plasma levels of malondialdehyde (P
AP = 0.003, PPP = 1.6 × 10-4 ) and protein carbonyls (PAP = 1.2 × 10-4 , PPP = 3.0 × 10-5 ) over 6 weeks. Nitrotyrosine (NT) increased upon both AP and PP diets (PAP = 0.005, PPP = 0.004). SAT expression of genes involved in nitric oxide (NO) and oxidative stress metabolism and urine NO metabolite (nitrate/nitrite) levels were not changed upon both diets. Plasma levels of carotenoids increased upon PP diet, whereas retinol, alpha- and gamma-tocopherol slightly decreased upon both diets. AP and PP diets similarly improve oxidative stress but increase nitrosative stress markers in individuals with T2DM. Mechanisms of the NT regulation upon high-protein diets need further investigation., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2020
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26. Reproducibility of novel immune-inflammatory biomarkers over 4 months: an analysis with repeated measures design.
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Schenk M, Eichelmann F, Schulze MB, Rudovich N, Pfeiffer AF, di Giuseppe R, Boeing H, and Aleksandrova K
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- Adult, Aged, Body Mass Index, Clusterin blood, Female, Humans, Inflammation blood, Inflammation immunology, Limit of Detection, Male, Middle Aged, Time Factors, Transforming Growth Factor beta blood, Waist Circumference, Blood Chemical Analysis methods
- Abstract
Aim: Assessment of the feasibility and reliability of immune-inflammatory biomarker measurements. Methods: The following biomarkers were assessed in 207 predominantly healthy participants at baseline and after 4 months: MMF, TGF-β, suPAR and clusterin. Results: Intraclass correlation coefficients (95% CIs) ranged from good for TGF-β (0.75 [95% CI: 0.33-0.90]) to excellent for MMF (0.81 [95% CI: 0.64-0.90]), clusterin (0.83 [95% CI: 0.78-0.87]) and suPAR (0.91 [95% CI: 0.88-0.93]). Measurement of TGF-β was challenged by the large number of values below the detection limit. Conclusion: Single measurements of suPAR, clusterin and MMF could serve as feasible and reliable biomarkers of immune-inflammatory pathways in biomedical research.
- Published
- 2019
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27. Diurnal distribution of carbohydrates and fat affects substrate oxidation and adipokine secretion in humans.
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Kessler K, Hornemann S, Petzke KJ, Kemper M, Markova M, Rudovich N, Grune T, Kramer A, Pfeiffer AFH, and Pivovarova-Ramich O
- Subjects
- Adult, Biomarkers blood, Body Mass Index, Cross-Over Studies, Cytokines blood, Dietary Carbohydrates metabolism, Dietary Fats metabolism, Fasting, Glucose Intolerance metabolism, Humans, Inflammation blood, Leptin blood, Lipids blood, Male, Middle Aged, Nicotinamide Phosphoribosyltransferase blood, Oxidation-Reduction, Postprandial Period, Adipokines metabolism, Circadian Rhythm physiology, Dietary Carbohydrates administration & dosage, Dietary Fats administration & dosage, Energy Metabolism drug effects
- Abstract
Background: A diet in which fat is mainly eaten in the morning and carbohydrates mainly in the evening (compared with the reverse order) was recently shown to worsen glycemic control in people with prediabetes., Objective: We investigated the effects of these dietary patterns on energy metabolism, and on the daily profiles of circulating lipids, adipokines, and inflammatory markers., Design: In a randomized controlled crossover trial, 29 nonobese men (with normal glucose tolerance, n = 18; or impaired fasting glucose/glucose tolerance, n = 11) underwent 2 isocaloric 4-wk diets: 1) carbohydrate-rich meals until 1330 and fat-rich meals between 1630 and 2200 (HC/HF); or 2) the inverse sequence of meals (HF/HC). During a 12-h clinical investigation day after each intervention period, 2 meal tolerance tests were performed, at 0900 and 1540, respectively. Substrate oxidation and concentrations of circulating lipids, adipokines, and cytokines were assessed pre- and postprandially. The postprandial inflammatory response in leukocytes was analyzed ex vivo., Results: Fasting carbohydrate oxidation decreased (P = 0.004) and lipid oxidation increased (P = 0.012) after the HC/HF diet. Fasting concentrations of blood markers did not differ between diets. The diets modulated the daily profiles of carbohydrate oxidation, lipid oxidation, and β-hydroxybutyrate, although the average daily values of these parameters showed no difference between the diets, and no interaction between diet and glucose tolerance status. Diurnal patterns of triglycerides, low-density lipoprotein cholesterol, leptin, visfatin, and of LPS-induced cytokine secretion in blood leukocytes were also modulated by the diets. Average daily concentrations of leptin (P = 0.017) and visfatin (P = 0.041) were lower on the HF/HC diet than on the HC/HF diet., Conclusions: Diurnal distribution of carbohydrates and fat affects the daily profiles of substrate oxidation, circulating lipids, and cytokine secretion, and alters the average daily concentrations of adipokine secretion in nonobese nondiabetic humans. The study was registered at clinicaltrials.gov as NCT02487576.
- Published
- 2018
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28. Assessment of circulating Wnt1 inducible signalling pathway protein 1 (WISP-1)/CCN4 as a novel biomarker of obesity.
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Tacke C, Aleksandrova K, Rehfeldt M, Murahovschi V, Markova M, Kemper M, Hornemann S, Kaiser U, Honig C, Gerbracht C, Kabisch S, Hörbelt T, Ouwens DM, Weickert MO, Boeing H, Pfeiffer AFH, Pivovarova O, and Rudovich N
- Abstract
WNT1 inducible signaling pathway protein 1 (WISP-1/CCN4) is a novel adipokine, which is upregulated in obesity, and induces a pro-inflammatory response in macrophages in-vitro. Preclinical observations suggested WISP-1/CCN4 as a potential candidate for novel obesity therapy targeting adipose tissue inflammation. Whether circulating levels of WISP-1/CCN4 in humans are altered in obesity and/or type 2 diabetes (T2DM) and in the postprandial state, however, is unknown. This study assessed circulating WISP-1/CCN4 levels in a) paired liquid meal tests and hyperinsulinemic- euglycemic clamps (cohort I, n = 26), b) healthy individuals (cohort II, n = 207) and c) individuals with different stages of obesity and glucose tolerance (cohort III, n = 253). Circulating plasma and serum WISP-1/CCN4 concentrations were measured using a commercially available ELISA. WISP-1/CCN4 levels were not influenced by changes in insulin and/or glucose during the tests. In healthy individuals, WISP-1/CCN4 was detectable in 13% of plasma samples with the intraclass correlation coefficient of 0.93 (95% CI: 0.84-0.96) and in 58.1% of the serum samples in cohort III. Circulating WISP-1/CCN4 positively correlated with body mass index, body fat percentage, leptin and triglyceride levels, hip circumference and fatty liver index. No differences in WISP-1/CCN4 levels between individuals with normal glucose tolerance, impaired glucose tolerance and T2DM were found. The circulating concentrations of WISP-1/CCN4 showed no acute regulation in postprandial state and correlated with anthropometrical obesity markers and lipid profiles. In healthy individuals, WISP-1/CCN4 levels are more often below the detection limit. Thus, serum WISP-1/CCN4 levels may be used as a suitable biomarker of obesity.
- Published
- 2018
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29. The novel adipokine WISP1 associates with insulin resistance and impairs insulin action in human myotubes and mouse hepatocytes.
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Hörbelt T, Tacke C, Markova M, Herzfeld de Wiza D, Van de Velde F, Bekaert M, Van Nieuwenhove Y, Hornemann S, Rödiger M, Seebeck N, Friedl E, Jonas W, Thoresen GH, Kuss O, Rosenthal A, Lange V, Pfeiffer AFH, Schürmann A, Lapauw B, Rudovich N, Pivovarova O, and Ouwens DM
- Subjects
- Animals, Blood Glucose metabolism, CCN Intercellular Signaling Proteins blood, Enzyme-Linked Immunosorbent Assay, Humans, Intra-Abdominal Fat metabolism, Mice, Phosphorylation, Proto-Oncogene Proteins blood, Receptor, Insulin metabolism, Signal Transduction, CCN Intercellular Signaling Proteins metabolism, Hepatocytes metabolism, Insulin Resistance physiology, Muscle Fibers, Skeletal metabolism, Proto-Oncogene Proteins metabolism
- Abstract
Aims/hypothesis: Wingless-type (Wnt) inducible signalling pathway protein-1 (WISP1) has been recently identified as a proinflammatory adipokine. We examined whether WISP1 expression and circulating levels are altered in type 2 diabetes and whether WISP1 affects insulin signalling in muscle cells and hepatocytes., Methods: Serum and visceral adipose tissue (VAT) biopsies, for analysis of circulating WISP1 levels by ELISA and WISP1 mRNA expression by real-time quantitative RT-PCR, were collected from normal-weight men (control group, n = 33) and obese men with (n = 46) and without type 2 diabetes (n = 56) undergoing surgery. Following incubation of primary human skeletal muscle cells (hSkMCs) and murine AML12 hepatocytes with WISP1 and insulin, insulin signalling was analysed by western blotting. The effect of WISP1 on insulin-stimulated glycogen synthesis and gluconeogenesis was investigated in hSkMCs and murine hepatocytes, respectively., Results: Circulating WISP1 levels were higher in obese men (independent of diabetes status) than in normal-weight men (mean [95% CI]: 70.8 [55.2, 86.4] ng/l vs 42.6 [28.5, 56.6] ng/l, respectively; p < 0.05). VAT WISP1 expression was 1.9-fold higher in obese men vs normal-weight men (p < 0.05). Circulating WISP1 levels were positively associated with blood glucose in the OGTT and circulating haem oxygenase-1 and negatively associated with adiponectin levels. In hSkMCs and AML12 hepatocytes, recombinant WISP1 impaired insulin action by inhibiting phosphorylation of insulin receptor, Akt and its substrates glycogen synthase kinase 3β, FOXO1 and p70S6 kinase, and inhibiting insulin-stimulated glycogen synthesis and suppression of gluconeogenic genes., Conclusions/interpretation: Circulating WISP1 levels and WISP1 expression in VAT are increased in obesity independent of glycaemic status. Furthermore, WISP1 impaired insulin signalling in muscle and liver cells.
- Published
- 2018
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30. Rate of appearance of amino acids after a meal regulates insulin and glucagon secretion in patients with type 2 diabetes: a randomized clinical trial.
- Author
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Markova M, Hornemann S, Sucher S, Wegner K, Pivovarova O, Rudovich N, Thomann R, Schneeweiss R, Rohn S, and Pfeiffer AFH
- Subjects
- Aged, Blood Glucose analysis, Female, Gastric Inhibitory Polypeptide blood, Glucagon-Like Peptide 1 analysis, Humans, Male, Middle Aged, Amino Acids blood, Diabetes Mellitus, Type 2 metabolism, Diet, High-Protein, Glucagon metabolism, Insulin metabolism
- Abstract
Background: Meal composition regulates the postprandial response of pancreatic and gastrointestinal hormones and plays an important role in patients with type 2 diabetes (T2D). Proteins have glucagon and insulinotropic effects, which may differ depending on amino acid composition, form of intake, and rate of digestibility and absorption., Objective: The aim of this study was to test effects of isolated pea protein-based (PP) compared with casein protein-based (CP) meals differing in amino acid compositions on endocrine responses to meal tolerance tests (MTTs) in patients with T2D., Design: Thirty-seven individuals with T2D [mean ± SD age: 64 ± 6 y; mean ± SD body mass index (kg/m2): 30.2 ± 3.6; mean ± SD glycated hemoglobin: 7.0% ± 0.6%] were randomly assigned to receive either high-animal-protein (∼80% of total protein) or high-plant-protein (∼72% of total protein) diets (30% of energy from protein, 40% of energy from carbohydrate, 30% of energy from fat) for 6 wk. MTTs were performed at study onset and after 6 wk. Participants received standardized high-protein (30% of energy) meals 2 times/d containing either CP-rich (∼85% wt:wt) or PP-rich (∼95% wt:wt) foods., Results: The CP and PP meals produced differences in insulin, C-peptide, glucagon, and glucose-dependent insulinotropic peptide (GIP) release. Total areas under the curve after CP were significantly lower than after the PP lunch by 40% for insulin and 23% for glucagon. Indexes of insulin sensitivity and secretion were significantly improved for the second CP MTT. This was accompanied by differential rates of appearance of amino acids. The ingestion of PP resulted in significant increases in amino acids after both meals, with a decline between meals. By contrast, CP intake resulted in increases in most amino acids after breakfast, which remained elevated but did not increase further after lunch., Conclusions: PP elicits greater postprandial increases in glucagon than does CP and consequently requires higher insulin to control glucose metabolism, which appears to be related to the rate of amino acid appearance. The metabolic impact of protein quality could be used as a strategy to lower insulin needs in patients with T2D. This trial was registered at www.clinicaltrials.gov as NCT02402985.
- Published
- 2018
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31. Effects of supplemented isoenergetic diets varying in cereal fiber and protein content on the bile acid metabolic signature and relation to insulin resistance.
- Author
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Weickert MO, Hattersley JG, Kyrou I, Arafat AM, Rudovich N, Roden M, Nowotny P, von Loeffelholz C, Matysik S, Schmitz G, and Pfeiffer AFH
- Subjects
- Dietary Fiber administration & dosage, Dietary Proteins administration & dosage, Edible Grain, Energy Intake, Fasting, Female, Fibroblast Growth Factors blood, Glucose Clamp Technique, Humans, Insulin blood, Liver drug effects, Liver metabolism, Male, Middle Aged, Milk Proteins administration & dosage, Milk Proteins pharmacology, Obesity complications, Overweight, Bile Acids and Salts blood, Body Mass Index, Diet, Dietary Fiber pharmacology, Dietary Proteins pharmacology, Insulin Resistance, Obesity blood
- Abstract
Bile acids (BA) are potent metabolic regulators influenced by diet. We studied effects of isoenergetic increases in the dietary protein and cereal-fiber contents on circulating BA and insulin resistance (IR) in overweight and obese adults. Randomized controlled nutritional intervention (18 weeks) in 72 non-diabetic participants (overweight/obese: 29/43) with at least one further metabolic risk factor. Participants were group-matched and allocated to four isoenergetic supplemented diets: control; high cereal fiber (HCF); high-protein (HP); or moderately increased cereal fiber and protein (MIX). Whole-body IR and insulin-mediated suppression of hepatic endogenous glucose production were measured using euglycaemic-hyperinsulinemic clamps with [6-6
2 H2 ] glucose infusion. Circulating BA, metabolic biomarkers, and IR were measured at 0, 6, and 18 weeks. Under isoenergetic conditions, HP-intake worsened IR in obese participants after 6 weeks (M-value: 3.77 ± 0.58 vs. 3.07 ± 0.44 mg/kg/min, p = 0.038), with partial improvement back to baseline levels after 18 weeks (3.25 ± 0.45 mg/kg/min, p = 0.089). No deleterious effects of HP-intake on IR were observed in overweight participants. HCF-diet improved IR in overweight participants after 6 weeks (M-value 4.25 ± 0.35 vs. 4.81 ± 0.31 mg/kg/min, p = 0.016), but did not influence IR in obese participants. Control and MIX diets did not influence IR. HP-induced, but not HCF-induced changes in IR strongly correlated with changes of BA profiles. MIX-diet significantly increased most BA at 18 weeks in obese, but not in overweight participants. BA remained unchanged in controls. Pooled BA concentrations correlated with fasting fibroblast growth factor-19 (FGF-19) plasma levels (r = 0.37; p = 0.003). Higher milk protein intake was the only significant dietary predictor for raised total and primary BA in regression analyses (total BA, p = 0.017; primary BA, p = 0.011). Combined increased intake of dietary protein and cereal fibers markedly increased serum BA concentrations in obese, but not in overweight participants. Possible mechanisms explaining this effect may include compensatory increases of the BA pool in the insulin resistant, obese state; or defective BA transport.- Published
- 2018
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32. Comparison of the effects of diets high in animal or plant protein on metabolic and cardiovascular markers in type 2 diabetes: A randomized clinical trial.
- Author
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Sucher S, Markova M, Hornemann S, Pivovarova O, Rudovich N, Thomann R, Schneeweiss R, Rohn S, and Pfeiffer AFH
- Subjects
- Aged, Biomarkers blood, C-Reactive Protein analysis, Cardiovascular Diseases complications, Cardiovascular Diseases epidemiology, Cohort Studies, Dairy Products adverse effects, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 metabolism, Diabetic Angiopathies epidemiology, Diabetic Cardiomyopathies epidemiology, Female, Germany epidemiology, Humans, Hypercholesterolemia complications, Hypercholesterolemia epidemiology, Hypercholesterolemia prevention & control, Hyperglycemia prevention & control, Male, Meat adverse effects, Middle Aged, Plant Proteins, Dietary adverse effects, Risk Factors, Uric Acid blood, Cardiovascular Diseases prevention & control, Diabetes Mellitus, Type 2 diet therapy, Diabetic Angiopathies prevention & control, Diabetic Cardiomyopathies prevention & control, Diet, Diabetic methods, Insulin Resistance, Plant Proteins, Dietary administration & dosage
- Abstract
Aim: To compare high animal protein (AP) with high plant protein (PP) diets, differing in amino acid composition, in people with type 2 diabetes (T2DM)., Materials and Methods: We compared isocaloric diets containing 30% of energy either as AP or PP, using newly developed PP-enriched foods, both combined with 30% energy as fat and 40% as carbohydrates in 44 patients with T2DM over 6 weeks in a randomized parallel-group study. Insulin sensitivity was assessed by hyperinsulinaemic-euglycaemic clamps and cardiovascular variables were measured., Results: Uric acid decreased in both groups, but significantly more in the AP than the PP group. There were no significant differences in other variables, although glycated haemoglobin levels, diastolic blood pressure and fasting non-esterified fatty acid levels improved significantly in the PP but not in the AP group. Insulin sensitivity (M-value), C-reactive protein and fasting glucose improved significantly in the AP but not in the PP group. Total and LDL cholesterol levels and systolic blood pressure decreased significantly in both groups, and the urinary albumin excretion rate decreased from baseline in participants with microalbuminuria., Conclusions: Isocaloric diets high in AP or PP allow similar improvements in metabolism and cardiovascular risk factors in people with T2DM, indicating that the differences in amino acid composition do not affect the metabolic responses to the interventions., (© 2017 John Wiley & Sons Ltd.)
- Published
- 2017
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33. ANGPTL8 (Betatrophin) is Expressed in Visceral Adipose Tissue and Relates to Human Hepatic Steatosis in Two Independent Clinical Collectives.
- Author
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von Loeffelholz C, Pfeiffer AFH, Lock JF, Lieske S, Döcke S, Murahovschi V, Kriebel J, de Las Heras Gala T, Grallert H, Rudovich N, Stockmann M, Spranger J, Jahreis G, Bornstein SR, Lau G, Xu A, Schulz-Menger J, Exner L, Haufe S, Jordan J, Engeli S, and Birkenfeld AL
- Subjects
- Angiopoietin-Like Protein 8, Angiopoietin-like Proteins metabolism, Cohort Studies, Diet, Female, Humans, Male, Middle Aged, Non-alcoholic Fatty Liver Disease genetics, Peptide Hormones metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Angiopoietin-like Proteins genetics, Fatty Liver genetics, Intra-Abdominal Fat metabolism, Peptide Hormones genetics
- Abstract
Angiopoietin-like protein 8 (ANGPTL8)/betatrophin expression in visceral adipose tissue and associations with circulating fatty acid profile have not yet been investigated.Forty subjects were included in a cross-sectional study, 57 in a dietary weight reduction intervention. Circulating Angiopoietin-like protein 8/betatrophin was measured in all subjects. Liver and adipose tissue were sampled and plasma fatty acids and tissue Angiopoietin-like protein 8/betatrophin expression were evaluated in the cross-sectional study. In the intervention study oral glucose testing and liver magnetic resonance scanning at baseline and after 6 months were performed. Angiopoietin-like protein 8/betatrophin mRNA was increased in visceral compared to subcutaneous adipose tissue (p<0.001). Circulating ANGPTL8/betatrophin correlated with liver steatosis (r=0.42, p=0.047), triacylglycerols (r=0.34, p=0.046), saturated (r=0.43, p=0.022), monounsaturated (r=0.51, p=0.007), and polyunsaturated fatty acids (r=-0.53, p=0.004). In the intervention study, baseline Angiopoietin-like protein 8/betatrophin correlated with age (r=0.32, p=0.010) and triacylglycerols (r=0.30, p=0.02) and was increased with hepatic steatosis (p=0.033). Weight loss reduced liver fat by 45% and circulating Angiopoietin-like protein 8/betatrophin by 11% (288±17 vs. 258±17 pg/ml; p=0.015). Angiopoietin-like protein 8/betatrophin is related to liver steatosis, while visceral adipose tissue represents an additional site of expression in humans., (© Georg Thieme Verlag KG Stuttgart · New York.)
- Published
- 2017
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34. The effect of diurnal distribution of carbohydrates and fat on glycaemic control in humans: a randomized controlled trial.
- Author
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Kessler K, Hornemann S, Petzke KJ, Kemper M, Kramer A, Pfeiffer AF, Pivovarova O, and Rudovich N
- Subjects
- Adolescent, Adult, Aged, Female, Glucose Tolerance Test, Humans, Male, Middle Aged, Blood Glucose metabolism, Dietary Carbohydrates administration & dosage, Dietary Fats administration & dosage, Fasting blood, Glucagon-Like Peptide 1 blood, Peptide YY blood
- Abstract
Diurnal carbohydrate and fat distribution modulates glycaemic control in rodents. In humans, the optimal timing of both macronutrients and its effects on glycaemic control after prolonged consumption are not studied in detail. In this cross-over trial, 29 non-obese men were randomized to two four-week diets: (1) carbohydrate-rich meals until 13.30 and fat-rich meals between 16.30 and 22.00 (HC/HF) versus (2) inverse sequence of meals (HF/HC). After each trial period two meal tolerance tests were performed, at 09.00 and 15.40, respectively, according to the previous intervention. On the HF/HC diet, whole-day glucose level was increased by 7.9% (p = 0.026) in subjects with impaired fasting glucose and/or impaired glucose tolerance (IFG/IGT, n = 11), and GLP-1 by 10.2% (p = 0.041) in normal glucose-tolerant subjects (NGT, n = 18). Diet effects on fasting GLP-1 (p = 0.009) and PYY (p = 0.034) levels were observed in IFG/IGT, but not in NGT. Afternoon decline of glucose tolerance was more pronounced in IFG/IGT and associated with a stronger decrease of postprandial GLP-1 and PYY levels, but not with changes of cortisol rhythm. In conclusion, the HF/HC diet shows an unfavourable effect on glycaemic control in IFG/IGT, but not in NGT subjects. Consequently, large, carbohydrate-rich dinners should be avoided, primarily by subjects with impaired glucose metabolism.
- Published
- 2017
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35. Isocaloric Diets High in Animal or Plant Protein Reduce Liver Fat and Inflammation in Individuals With Type 2 Diabetes.
- Author
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Markova M, Pivovarova O, Hornemann S, Sucher S, Frahnow T, Wegner K, Machann J, Petzke KJ, Hierholzer J, Lichtinghagen R, Herder C, Carstensen-Kirberg M, Roden M, Rudovich N, Klaus S, Thomann R, Schneeweiss R, Rohn S, and Pfeiffer AF
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- Adiponectin metabolism, Adipose Tissue, Aged, Animals, Body Composition, Chemokine CCL2 metabolism, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 metabolism, Dietary Proteins, Down-Regulation, Energy Metabolism, Enzyme-Linked Immunosorbent Assay, Female, Fibroblast Growth Factors metabolism, Glucose Clamp Technique, Humans, Inflammation, Insulin metabolism, Insulin Resistance, Interleukin-18 metabolism, Lipid Metabolism, Lipogenesis, Liver metabolism, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Male, Middle Aged, Non-alcoholic Fatty Liver Disease complications, Non-alcoholic Fatty Liver Disease diagnostic imaging, Non-alcoholic Fatty Liver Disease metabolism, Prospective Studies, Dairy Products, Diabetes Mellitus, Type 2 drug therapy, Hypoglycemic Agents therapeutic use, Liver diagnostic imaging, Meat, Non-alcoholic Fatty Liver Disease diet therapy, Plant Proteins, Dietary therapeutic use
- Abstract
Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is associated with increased risk of hepatic, cardiovascular, and metabolic diseases. High-protein diets, rich in methionine and branched chain amino acids (BCAAs), apparently reduce liver fat, but can induce insulin resistance. We investigated the effects of diets high in animal protein (AP) vs plant protein (PP), which differ in levels of methionine and BCAAs, in patients with type 2 diabetes and NAFLD. We examined levels of liver fat, lipogenic indices, markers of inflammation, serum levels of fibroblast growth factor 21 (FGF21), and activation of signaling pathways in adipose tissue., Methods: We performed a prospective study of individuals with type 2 diabetes and NAFLD at a tertiary medical center in Germany from June 2013 through March 2015. We analyzed data from 37 subjects placed on a diet high in AP (rich in meat and dairy foods; n = 18) or PP (mainly legume protein; n = 19) without calorie restriction for 6 weeks. The diets were isocaloric with the same macronutrient composition (30% protein, 40% carbohydrates, and 30% fat). Participants were examined at the start of the study and after the 6-week diet period for body mass index, body composition, hip circumference, resting energy expenditure, and respiratory quotient. Body fat and intrahepatic fat were detected by magnetic resonance imaging and spectroscopy, respectively. Levels of glucose, insulin, liver enzymes, and inflammation markers, as well as individual free fatty acids and free amino acids, were measured in collected blood samples. Hyperinsulinemic euglycemic clamps were performed to determine whole-body insulin sensitivity. Subcutaneous adipose tissue samples were collected and analyzed for gene expression patterns and phosphorylation of signaling proteins., Results: Postprandial levels of BCAAs and methionine were significantly higher in subjects on the AP vs the PP diet. The AP and PP diets each reduced liver fat by 36%-48% within 6 weeks (for AP diet P = .0002; for PP diet P = .001). These reductions were unrelated to change in body weight, but correlated with down-regulation of lipolysis and lipogenic indices. Serum level of FGF21 decreased by 50% in each group (for AP diet P < .0002; for PP diet P < .0002); decrease in FGF21 correlated with loss of hepatic fat. In gene expression analyses of adipose tissue, expression of the FGF21 receptor cofactor β-klotho was associated with reduced expression of genes encoding lipolytic and lipogenic proteins. In patients on each diet, levels of hepatic enzymes and markers of inflammation decreased, insulin sensitivity increased, and serum level of keratin 18 decreased., Conclusions: In a prospective study of patients with type 2 diabetes, we found diets high in protein (either animal or plant) significantly reduced liver fat independently of body weight, and reduced markers of insulin resistance and hepatic necroinflammation. The diets appear to mediate these changes via lipolytic and lipogenic pathways in adipose tissue. Negative effects of BCAA or methionine were not detectable. FGF21 level appears to be a marker of metabolic improvement. ClinicalTrials.gov ID NCT02402985., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)
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- 2017
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36. Modulation of circulating vasoactive peptides and extracellular matrix proteins are two novel mechanisms in the cardioprotective action of acarbose.
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Rudovich N, Pivovarova O, Bernigau W, Sparwasser A, Tacke C, Murahovshi V, Mertes G, Birkenfeld AL, Bergmann A, Weickert MO, and Pfeiffer AF
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- Cross-Over Studies, Diabetes Mellitus, Type 2 blood, Double-Blind Method, Female, Humans, Insulin blood, Male, Metabolic Syndrome blood, Middle Aged, Acarbose therapeutic use, Cardiotonic Agents therapeutic use, Extracellular Matrix Proteins blood, Vasoactive Intestinal Peptide blood
- Abstract
Background: Acarbose, an alpha-glucosidase inhibitor, unexpectedly reduced the incidence of hypertension and cardiovascular endpoints in the STOP-NIDDM study. Based on the growing evidence of a link between vasoregulatory peptides and metabolic traits, we hypothesized that changes of the Glycemic Index by acarbose may modulate vasoregulatory peptide levels via regulation of postprandial metabolism., Methods: Subjects with type 2 diabetes and with metabolic syndrome were treated with acarbose (12 weeks, 300mg/d) in a double-blind, placebo-controlled, cross-over intervention. Changes in fasting and postprandial levels of midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1) and midregional pro-adrenomedullin (MR-proADM), WNT1 Inducible Signaling Pathway Protein 1 (WISP1) as well as fasting and postprandial glucose/insulin levels in the liquid meal test were assessed., Results: Acarbose strongly decreased postprandial insulin concentrations in subjects with metabolic syndrome (P=0.004), and postprandial glucose excursions in both groups. Postprandial MR-proANP and CT-proET-1 levels increased after acarbose treatment (P<0.01 and P<0.05, respectively) in subjects with metabolic syndrome only. No effect of acarbose treatment on MR-prADM was observed in both groups. All three peptides were correlated with each over, but neither with insulin sensitivity in euglycemic clamps, nor with adiponectin levels. WISP1 decreased after acarbose treatment in subjects with metabolic syndrome., Conclusions: Plasma MR- proANP and CT-proET-1 concentrations, but not MR-prADM concentrations, were affected by treatment with acarbose over 12 weeks. Our findings provide new possible mechanisms of acarbose action in diabetes and metabolic syndrome.
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- 2016
37. Insulin-degrading enzyme: new therapeutic target for diabetes and Alzheimer's disease?
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Pivovarova O, Höhn A, Grune T, Pfeiffer AF, and Rudovich N
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- Alzheimer Disease enzymology, Alzheimer Disease metabolism, Animals, Diabetes Mellitus, Type 2 metabolism, Disease Models, Animal, Drug Evaluation, Preclinical, Enzyme Inhibitors pharmacology, Humans, Mice, Molecular Targeted Therapy, Alzheimer Disease drug therapy, Diabetes Mellitus, Type 2 drug therapy, Enzyme Inhibitors therapeutic use, Insulysin antagonists & inhibitors
- Abstract
Insulin-degrading enzyme (IDE) is a major enzyme responsible for insulin degradation. In addition to insulin, IDE degrades many targets including glucagon, atrial natriuretic peptide, and beta-amyloid peptide, regulates proteasomal degradation and other cell functions. IDE represents a pathophysiological link between type 2 diabetes (T2DM) and late onset Alzheimer's disease (AD). Potent and selective modulators of IDE activity are potential drugs for therapies of both diseases. Acute treatment with a novel IDE inhibitor was recently tested in a mouse study as a therapeutic approach for the treatment of T2DM. In contrast, effective IDE activators can be used for the AD treatment. However, because of the pleiotropic IDE action, the sustained treatment with systemic IDE modulators should be carefully tested in animal studies. Development of substrate-selective IDE modulators could overcome possible adverse effects of IDE modulators associated with multiplicity of IDE targets. KEY MESSAGES Insulin-degrading enzyme (IDE) represents a pathophysiological link between type 2 diabetes (T2DM) and Alzheimer's disease (AD). Selective modulators of IDE activity are potential drugs for both T2DM and AD treatment. Development of substrate-selective IDE modulators could overcome possible adverse effects of IDE modulators associated with multiplicity of IDE targets.
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- 2016
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38. Effects of Palatinose and Sucrose Intake on Glucose Metabolism and Incretin Secretion in Subjects With Type 2 Diabetes.
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Keyhani-Nejad F, Kemper M, Schueler R, Pivovarova O, Rudovich N, and Pfeiffer AF
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- 2016
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39. Diabetes prevalence in NZO females depends on estrogen action on liver fat content.
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Lubura M, Hesse D, Kraemer M, Hallahan N, Schupp M, von Löffelholz C, Kriebel J, Rudovich N, Pfeiffer A, John C, Scheja L, Heeren J, Koliaki C, Roden M, and Schürmann A
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- Animals, Female, Intra-Abdominal Fat drug effects, Liver drug effects, Prevalence, Rats, Diabetes Mellitus, Type 2 metabolism, Estrogens pharmacology, Fatty Acids metabolism, Intra-Abdominal Fat metabolism, Liver metabolism, Obesity metabolism
- Abstract
In humans and rodents, risk of metabolic syndrome is sexually dimorphic, with an increased incidence in males. Additionally, the protective role of female gonadal hormones is ostensible, as prevalence of type 2 diabetes mellitus (T2DM) increases after menopause. Here, we investigated the influence of estrogen (E2) on the onset of T2DM in female New Zealand obese (NZO) mice. Diabetes prevalence (defined as blood glucose levels >16.6 mmol/l) of NZO females on high-fat diet (60 kcal% fat) in week 22 was 43%. This was markedly dependent on liver fat content in week 10, as detected by computed tomography. Only mice with a liver fat content >9% in week 10 plus glucose levels >10 mmol/l in week 9 developed hyperglycemia by week 22. In addition, at 11 wk, diacylglycerols were elevated in livers of diabetes-prone mice compared with controls. Hepatic expression profiles obtained from diabetes-prone and -resistant mice at 11 wk revealed increased abundance of two transcripts in diabetes-prone mice: Mogat1, which catalyzes the synthesis of diacylglycerols from monoacylglycerol and fatty acyl-CoA, and the fatty acid transporter Cd36. E2 treatment of diabetes-prone mice for 10 wk prevented any further increase in liver fat content and reduced diacylglycerols and the abundance of Mogat1 and Cd36, leading to a reduction of diabetes prevalence and an improved glucose tolerance compared with untreated mice. Our data indicate that early elevation of hepatic Cd36 and Mogat1 associates with increased production and accumulation of triglycerides and diacylglycerols, presumably resulting in reduced hepatic insulin sensitivity and leading to later onset of T2DM., (Copyright © 2015 the American Physiological Society.)
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- 2015
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40. GIP increases adipose tissue expression and blood levels of MCP-1 in humans and links high energy diets to inflammation: a randomised trial.
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Gögebakan Ö, Osterhoff MA, Schüler R, Pivovarova O, Kruse M, Seltmann AC, Mosig AS, Rudovich N, Nauck M, and Pfeiffer AF
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- Adipocytes drug effects, Adipocytes metabolism, Adipose Tissue metabolism, Adolescent, Adult, Aged, Cells, Cultured, Chemokine CCL2 blood, Chemokine CCL2 genetics, Cross-Over Studies, Gastric Inhibitory Polypeptide blood, Humans, Inflammation blood, Insulin blood, Male, Middle Aged, Signal Transduction drug effects, Single-Blind Method, Young Adult, Adipose Tissue drug effects, Chemokine CCL2 metabolism, Diet, Gastric Inhibitory Polypeptide pharmacology, Gene Expression drug effects, Inflammation metabolism, Obesity metabolism
- Abstract
Aims/hypothesis: Obesity is associated with elevated monocyte chemoattractant protein-1 (MCP-1), a proinflammatory chemokine related to diabetes and cardiovascular disease. Since obesity is triggered by energy dense diets, we hypothesised that nutrient induced intestinal hormones such as glucose-dependent insulinotropic peptide (GIP) may directly stimulate the release of chemokines from adipose tissue and induce low-grade inflammation., Methods: GIP effects on gene expression and secretion of inflammatory markers were studied by microarray analysis and PCR from human subcutaneous fat biopsies of slightly obese but healthy volunteers in the metabolic ward of German Institute of Human Nutrition, Department of Clinical Nutrition, Potsdam-Rehbrücke. To allocate the participants to the study arms they were numbered in order of their recruitment and then assigned to the groups by a random number generator. In a randomised, single-blind (participants) crossover design, the participants received GIP infusions in postprandial concentrations (2 pmol kg(-1) min(-1)) or saline (154 mmol/l NaCl) infusions for 240 min either alone, in combination with hyperinsulinaemic-euglycaemic (EU) or hyperinsulinaemic-hyperglycaemic (HC) clamps. Possible mechanisms of GIP effects were investigated in single and co-cultures of macrophage and adipocyte cell lines and in primary human monocytes, macrophages and adipocytes., Results: A total of 17 participants were randomised to the following groups: EU with GIP infusion (n = 9); EU with NaCl infusion (n = 9); HC with GIP infusion (n = 8); HC with NaCl infusion (n = 8); sole GIP infusion (n = 11) and sole placebo infusion (n = 11). All 17 individuals were analysed. The study is completed. In human subcutaneous adipose tissue (hSCAT), infusions of GIP significantly increased inflammatory chemokine and cytokine gene networks in transcriptomic microarray analyses. Particularly MCP-1 (180 ± 26%), MCP-2 (246 ± 58%) and IL-6 (234 ± 40%) mRNA levels in adipose tissue as well as circulating plasma concentrations of MCP-1 (165 ± 12 vs 135 ± 13 pg/ml; GIP vs saline after 240 min; p < 0.05 for all variables) in humans increased independently of circulating insulin or glucose plasma concentrations. GIP stimulation increased Mcp-1 mRNA-expression in co-cultures of differentiated 3T3L1-adipocytes and RAW 264.7 macrophages but not in the isolated cell lines. Similarly, GIP increased MCP-1 transcripts in co-cultures of primary human macrophages with human adipocytes. GIP receptor (GIPR) transcripts were present in primary monocytes and the different cell lines and induced activation of extracellular related kinase (ERK) as well as increases in cAMP, indicating functional receptors., Conclusions/interpretation: Our findings suggest that the nutrient induced gut hormone GIP may initiate adipose tissue inflammation by triggering a crosstalk of adipocytes and macrophages involving MCP-1., Trial Registration: ClinicalTrials.gov NCT00774488., Funding: This work was supported by the German Research Foundation (DFG): grant No. Pf164/021002.
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- 2015
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41. Changes of Dietary Fat and Carbohydrate Content Alter Central and Peripheral Clock in Humans.
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Pivovarova O, Jürchott K, Rudovich N, Hornemann S, Ye L, Möckel S, Murahovschi V, Kessler K, Seltmann AC, Maser-Gluth C, Mazuch J, Kruse M, Busjahn A, Kramer A, and Pfeiffer AF
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- Brain drug effects, Brain physiology, CLOCK Proteins genetics, Carbohydrate Metabolism drug effects, Circadian Clocks genetics, Circadian Rhythm drug effects, Circadian Rhythm genetics, Diet, Carbohydrate-Restricted, Diet, Fat-Restricted, Diet, High-Fat, Gene Expression Regulation drug effects, Humans, Hydrocortisone metabolism, Lipid Metabolism drug effects, Monocytes drug effects, Monocytes metabolism, Circadian Clocks drug effects, Dietary Carbohydrates pharmacology, Dietary Fats pharmacology
- Abstract
Context: The circadian clock coordinates numerous metabolic processes with light-dark and feeding regimens. However, in humans it is unknown whether dietary patterns influence circadian rhythms., Objective: We examined the effects of switching from a high-carbohydrate, low-fat diet to a low-carbohydrate, high fat (LC/HFD) isocaloric diet on the central and peripheral circadian clocks in humans., Design: Diurnal patterns of salivary cortisol and gene expression were analyzed in blood monocytes of 29 nonobese healthy subjects before and 1 and 6 weeks after the dietary switch. For this, we established a method of rhythm prediction by 3-time point data., Results: The centrally driven cortisol rhythm showed a phase delay 1 and 6 weeks after the dietary switch to a LC/HFD as well as an amplitude increase. The dietary switch altered diurnal oscillations of core clock genes (PER1, PER2, PER3, and TEF) and inflammatory genes (CD14, CD180, NFKBIA, and IL1B). The LC/HFD also affected the expression of nonoscillating genes contributing to energy metabolism (SIRT1) and fat metabolism (ACOX3 and IDH3A). Expression of clock genes but not of salivary cortisol in monocytes tightly correlated with levels of blood lipids and with expression of metabolic and inflammatory genes., Conclusions: Our results suggest that the modulation of the dietary fat and carbohydrate content alters the function of the central and peripheral circadian clocks in humans.
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- 2015
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42. Regulation of nutrition-associated receptors in blood monocytes of normal weight and obese humans.
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Pivovarova O, Hornemann S, Weimer S, Lu Y, Murahovschi V, Zhuk S, Seltmann AC, Malashicheva A, Kostareva A, Kruse M, Busjahn A, Rudovich N, and Pfeiffer AF
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- Adult, Case-Control Studies, Cholecystokinin genetics, Cholecystokinin metabolism, Diet, Fat-Restricted, Diet, High-Fat, Female, Humans, Incretins genetics, Incretins metabolism, Macrophages metabolism, Male, Monocytes metabolism, Neuropeptides genetics, Neuropeptides metabolism, Obesity blood, Organ Specificity, Primary Cell Culture, Receptors, Cell Surface genetics, Receptors, Cell Surface metabolism, Receptors, G-Protein-Coupled genetics, Receptors, G-Protein-Coupled metabolism, Receptors, Neurotensin genetics, Receptors, Neurotensin metabolism, Dietary Carbohydrates administration & dosage, Dietary Fats administration & dosage, Gene Expression Regulation drug effects, Macrophages drug effects, Monocytes drug effects, Obesity genetics
- Abstract
Obesity, type 2 diabetes and associated metabolic diseases are characterized by low-grade systemic inflammation which involves interplay of nutrition and monocyte/macrophage functions. We suggested that some factors such as nutrient components, neuropeptides involved in the control of gastrointestinal functions, and gastrointestinal hormones might influence immune cell functions and in this way contribute to the disease pathogenesis. The aim of this study was to investigate the mRNA expression of twelve nutrition-associated receptors in peripheral blood mononuclear cells (PBMC), isolated monocytes and monocyte-derived macrophages and their regulation under the switching from the high-carbohydrate low-fat diet to the low-carbohydrate high-fat (LC/HFD) isocaloric diet in healthy humans. The mRNA expression of receptors for short chain fatty acids (GPR41, GPR43), bile acids (TGR5), incretins (GIPR, GLP1R), cholecystokinin (CCKAR), neuropeptides VIP and PACAP (VIPR1, VIPR2), and neurotensin (NTSR1) was detected in PBMC and monocytes, while GPR41, GPR43, GIPR, TGR5, and VIPR1 were found in macrophages. Correlations of the receptor expression in monocytes with a range of metabolic and inflammatory markers were found. In non-obese subjects, the dietary switch to LC/HFD induced the increase of GPR43 and VIPR1 expression in monocytes. No significant differences of receptor expression between normal weight and moderately obese subjects were found. Our study characterized for the first time the expression pattern of nutrition-associated receptors in human blood monocytes and its dietary-induced changes linking metabolic responses to nutrition with immune functions in health and metabolic diseases., (Copyright © 2015 Elsevier Inc. All rights reserved.)
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- 2015
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43. WISP1 is a novel adipokine linked to inflammation in obesity.
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Murahovschi V, Pivovarova O, Ilkavets I, Dmitrieva RM, Döcke S, Keyhani-Nejad F, Gögebakan Ö, Osterhoff M, Kemper M, Hornemann S, Markova M, Klöting N, Stockmann M, Weickert MO, Lamounier-Zepter V, Neuhaus P, Konradi A, Dooley S, von Loeffelholz C, Blüher M, Pfeiffer AF, and Rudovich N
- Subjects
- Adipose Tissue metabolism, Animals, Blotting, Western, CCN Intercellular Signaling Proteins genetics, Cells, Cultured, Humans, Intra-Abdominal Fat metabolism, Macrophages metabolism, Magnetic Resonance Imaging, Male, Mesenchymal Stem Cells, Mice, Non-alcoholic Fatty Liver Disease metabolism, Proto-Oncogene Proteins genetics, Real-Time Polymerase Chain Reaction, Subcutaneous Fat metabolism, Adipokines metabolism, CCN Intercellular Signaling Proteins metabolism, Inflammation metabolism, Obesity metabolism, Proto-Oncogene Proteins metabolism
- Abstract
WISP1 (Wnt1-inducible signaling pathway protein-1, also known as CCN4) is a member of the secreted extracellular matrix-associated proteins of the CCN family and a target gene of the Wingless-type (WNT) signaling pathway. Growing evidence links the WNT signaling pathway to the regulation of adipogenesis and low-grade inflammation in obesity. We aimed to validate WISP1 as a novel adipokine. Human adipocyte differentiation was associated with increased WISP1 expression and secretion. Stimulation of human macrophages with WISP1 led to a proinflammatory response. Circulating WISP1 and WISP1 subcutaneous adipose tissue expression were regulated by weight changes in humans and mice. WISP1 expression in visceral and subcutaneous fat tissue was associated with markers of insulin resistance and inflammation in glucose-tolerant subjects. In patients with nonalcoholic fatty liver disease, we found no correlation among disease activity score, liver fat content, and WISP1 expression. Insulin regulated WISP1 expression in adipocytes in vitro but had no acute effect on WISP1 gene expression in subcutaneous fat tissue in overweight subjects who had undergone hyperinsulinemic clamp experiments. The data suggest that WISP1 may play a role in linking obesity to inflammation and insulin resistance and could be a novel therapeutic target for obesity., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)
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- 2015
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44. Modulation of insulin degrading enzyme activity and liver cell proliferation.
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Pivovarova O, von Loeffelholz C, Ilkavets I, Sticht C, Zhuk S, Murahovschi V, Lukowski S, Döcke S, Kriebel J, de las Heras Gala T, Malashicheva A, Kostareva A, Lock JF, Stockmann M, Grallert H, Gretz N, Dooley S, Pfeiffer AF, and Rudovich N
- Subjects
- Adult, Aged, Apoptosis drug effects, Cohort Studies, Cyclin G2 metabolism, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 pathology, Female, Gene Expression Profiling, Hep G2 Cells, Humans, Insulysin antagonists & inhibitors, Insulysin genetics, Ki-67 Antigen metabolism, Male, Middle Aged, Minichromosome Maintenance Complex Component 2 metabolism, Proliferating Cell Nuclear Antigen metabolism, RNA Interference, Transcriptome drug effects, fas Receptor metabolism, Cell Proliferation drug effects, Insulin pharmacology, Insulysin metabolism, Liver metabolism
- Abstract
Diabetes mellitus type 2 (T2DM), insulin therapy, and hyperinsulinemia are independent risk factors of liver cancer. Recently, the use of a novel inhibitor of insulin degrading enzyme (IDE) was proposed as a new therapeutic strategy in T2DM. However, IDE inhibition might stimulate liver cell proliferation via increased intracellular insulin concentration. The aim of this study was to characterize effects of inhibition of IDE activity in HepG2 hepatoma cells and to analyze liver specific expression of IDE in subjects with T2DM. HepG2 cells were treated with 10 nM insulin for 24 h with or without inhibition of IDE activity using IDE RNAi, and cell transcriptome and proliferation rate were analyzed. Human liver samples (n = 22) were used for the gene expression profiling by microarrays. In HepG2 cells, IDE knockdown changed expression of genes involved in cell cycle and apoptosis pathways. Proliferation rate was lower in IDE knockdown cells than in controls. Microarray analysis revealed the decrease of hepatic IDE expression in subjects with T2DM accompanied by the downregulation of the p53-dependent genes FAS and CCNG2, but not by the upregulation of proliferation markers MKI67, MCM2 and PCNA. Similar results were found in the liver microarray dataset from GEO Profiles database. In conclusion, IDE expression is decreased in liver of subjects with T2DM which is accompanied by the dysregulation of p53 pathway. Prolonged use of IDE inhibitors for T2DM treatment should be carefully tested in animal studies regarding its potential effect on hepatic tumorigenesis.
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- 2015
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45. Effect of exogenous intravenous administrations of GLP-1 and/or GIP on circulating pro-atrial natriuretic peptide in subjects with different stages of glucose tolerance.
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Rudovich N, Pivovarova O, Gögebakan Ö, Sparwasser A, Doehner W, Anker SD, Arafat AM, Bergmann A, Nauck MA, and Pfeiffer AF
- Subjects
- Administration, Intravenous, Aged, Female, Glucose Intolerance drug therapy, Humans, Male, Middle Aged, Overweight blood, Atrial Natriuretic Factor blood, Diabetes Mellitus, Type 2 blood, Gastric Inhibitory Polypeptide administration & dosage, Glucagon-Like Peptide 1 administration & dosage
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- 2015
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46. Hepatic insulin clearance is closely related to metabolic syndrome components.
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Pivovarova O, Bernigau W, Bobbert T, Isken F, Möhlig M, Spranger J, Weickert MO, Osterhoff M, Pfeiffer AF, and Rudovich N
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- Adult, Aged, Diabetes Mellitus, Type 2 blood, Fasting, Female, Glucose Tolerance Test, Humans, Insulin blood, Insulin Resistance, Male, Metabolic Syndrome blood, Metabolic Syndrome diagnosis, Middle Aged, Risk, Triglycerides blood, Waist Circumference, Diabetes Mellitus, Type 2 metabolism, Insulin metabolism, Liver metabolism, Metabolic Syndrome epidemiology
- Abstract
Objective: Insulin clearance is decreased in type 2 diabetes mellitus (T2DM) for unknown reasons. Subjects with metabolic syndrome are hyperinsulinemic and have an increased risk of T2DM. We aimed to investigate the relationship between hepatic insulin clearance (HIC) and different components of metabolic syndrome and tested the hypothesis that HIC may predict the risk of metabolic syndrome., Research Design and Methods: Individuals without diabetes from the Metabolic Syndrome Berlin Brandenburg (MeSyBePo) study (800 subjects with the baseline examination and 189 subjects from the MeSyBePo recall study) underwent an oral glucose tolerance test (OGTT) with assessment of insulin secretion (insulin secretion rate [ISR]) and insulin sensitivity. Two indices of HIC were calculated., Results: Both HIC indices showed lower values in subjects with metabolic syndrome (P < 0.001) at baseline. HIC indices correlate inversely with waist circumference, diastolic blood pressure, fasting glucose, triglycerides, and OGTT-derived insulin secretion index. During a mean follow-up of 5.1 ± 0.9 years, 47 individuals developed metabolic syndrome and 33 subjects progressed to impaired glucose metabolism. Both indices of HIC showed a trend of an association with increased risk of metabolic syndrome (HICC-peptide odds ratio 1.13 [95% CI 0.97-1.31], P = 0.12, and HICISR 1.38 [0.88-2.17], P = 0.16) and impaired glucose metabolism (HICC-peptide 1.12 [0.92-1.36], P = 0.26, and HICISR 1.31 [0.74-2.33] P = 0.36), although point estimates reached no statistical significance., Conclusions: HIC was associated with different components of metabolic syndrome and markers of insulin secretion and insulin sensitivity. Decreased HIC may represent a novel pathophysiological mechanism of the metabolic syndrome, which may be used additionally for early identification of high-risk subjects.
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- 2013
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47. In vivo effect of glucose-dependent insulinotropic peptide (GIP) on the gene expression of calcitonin peptides in human subcutaneous adipose tissue.
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Pivovarova O, Gögebakan O, Osterhoff MA, Nauck M, Pfeiffer AF, and Rudovich N
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- Adult, Blood Glucose, Calcitonin genetics, Calcitonin Gene-Related Peptide, Gastric Inhibitory Polypeptide blood, Glucose Clamp Technique methods, Humans, Hyperinsulinism metabolism, Insulin blood, Male, Middle Aged, Obesity genetics, Protein Precursors genetics, RNA, Messenger genetics, RNA, Messenger metabolism, Subcutaneous Fat drug effects, Waist-Hip Ratio, Calcitonin blood, Gastric Inhibitory Polypeptide pharmacology, Gene Expression Regulation, Obesity metabolism, Protein Precursors blood, Subcutaneous Fat metabolism
- Abstract
Background: Increased plasma levels of calcitonin gene-related peptide-I (CGRP-I) and procalcitonin (Pro-CT) (both also named calcitonin peptides (CT peptides)) are associated with obesity and systemic inflammation. Glucose-dependent insulinotropic polypeptide (GIP), a nutrient-dependent incretin hormone, was recently found to induce CGRP-I and CT expression in human adipocytes in vitro. However, a physiological relevance of a possible interaction between GIP and CT peptides has not yet been studied., Methods: In this study, we analyzed the effect of GIP on the expression of CGRP-I and CT mRNA in human subcutaneous adipose tissue within a randomized, controlled trial. Seventeen male obese subjects were infused with GIP [2.0 pmol kg(-1) min(-1) for 240 min] or placebo, either in the fasting state, during euglycemic-hyperinsulinemic (EC) or hyperglycemic-hyperinsulinemic clamps (HC)., Results: The CGRP-I gene expression was detected in all investigated adipose tissue samples, whereas very low CT expression was found in only 8 out of 116 analyzed samples. No significant influence of either GIP or glucose and insulin infusions on the CGRP-I and CT expression was observed in any of the individual experiments (GIP infusion, EC and HC) or in the combined analysis of all experiments with and without GIP. Furthermore, CGRP-I expression was not correlated with plasma GIP level before or after 240 min of infusions or clamps., Conclusion: In contrast to in vitro data, an acute application of GIP has no effect on mRNA expression of CT peptides in subcutaneous adipose tissue of obese humans., (Copyright © 2012 Elsevier B.V. All rights reserved.)
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- 2012
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48. Insulin up-regulates natriuretic peptide clearance receptor expression in the subcutaneous fat depot in obese subjects: a missing link between CVD risk and obesity?
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Pivovarova O, Gögebakan Ö, Klöting N, Sparwasser A, Weickert MO, Haddad I, Nikiforova VJ, Bergmann A, Kruse M, Seltmann AC, Blüher M, Pfeiffer AF, and Rudovich N
- Subjects
- Adult, Blood Glucose metabolism, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 metabolism, Female, Gene Expression drug effects, Gene Expression physiology, Humans, Insulin pharmacology, Insulin Resistance, Intra-Abdominal Fat drug effects, Intra-Abdominal Fat metabolism, Male, Obesity genetics, Receptors, Atrial Natriuretic Factor genetics, Subcutaneous Fat drug effects, Insulin metabolism, Obesity metabolism, Receptors, Atrial Natriuretic Factor metabolism, Subcutaneous Fat metabolism
- Abstract
Context: Natriuretic peptides (NP) regulate cardiovascular homeostasis and have multiple metabolic properties. Decreased levels of NP or "natriuretic handicap" are signs of insulin resistance such as central obesity. Increased expression of NP clearance receptor (NPRC) in sc adipose tissue (SAT) was observed in insulin-resistant subjects., Objective: We hypothesized that insulin acutely regulates NP receptor expression in adipose tissue., Design and Participants: NPRA, NPRB, and NPRC mRNA expression was measured in paired samples of visceral adipose tissue (VAT) and SAT from 157 subjects (108 with type 2 diabetes). The effect of insulin on NPR gene expression in SAT was studied in euglycemic-hyperinsulinemic and hyperglycemic-hyperinsulinemic clamp experiments. Additionally, the effect of insulin and glucose on NPR expression in the culture of primary human monocytes and macrophages was tested., Results: NPRA and NPRC gene expression was higher in VAT compared with SAT (P < 0.01), but only NPRC gene expression strongly correlated with fasting insulin levels (r = 0.65, P = 0.04 × 10(-3); and r = 0.54, P = 0.002, for VAT and SAT, respectively). NPRB expression was lower in VAT than in SAT in subjects with type 2 diabetes and was lower compared with nondiabetic subjects. NPRC gene expression was up-regulated in SAT during both euglycemic- and hyperglycemic-hyperinsulinemic clamps (P = 0.038 and P = 0.048, respectively), and was increased in high glucose and insulin treatment in monocytes (70.2%; P = 0.01), but not in mature macrophages., Conclusion: Insulin increased expression of NPRC in SAT independently of circulating glucose concentrations. Thus, insulin might suppress circulating NP via up-regulation of NPRC expression in obesity, providing a novel link between hyperinsulinemia and obesity.
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- 2012
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49. A polymorphism within the connective tissue growth factor (CTGF) gene has no effect on non-invasive markers of beta-cell area and risk of type 2 diabetes.
- Author
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Pivovarova O, Fisher E, Dudziak K, Ilkavets I, Dooley S, Slominsky P, Limborska S, Weickert MO, Spranger J, Fritsche A, Boeing H, Pfeiffer AF, and Rudovich N
- Subjects
- Adult, Aged, Blood Glucose, C-Peptide blood, Cohort Studies, Female, Gene Frequency, Genetic Association Studies, Genetic Markers, Genotype, Germany, Humans, Male, Middle Aged, Prospective Studies, Risk Factors, Sequence Analysis, DNA, Connective Tissue Growth Factor genetics, Diabetes Mellitus, Type 2 genetics, Insulin-Secreting Cells pathology, Polymorphism, Single Nucleotide
- Abstract
Chromosomal locus 6q23 is strongly linked to type 2 diabetes (T2DM) and related features including insulin secretion in various ethnic populations. Connective tissue growth factor (CTGF) gene is an interesting T2DM candidate gene in this chromosome region. CTGF is a key mediator of progressive pancreatic fibrosis up-regulated in type 2 diabetes. In contrast, CTGF inactivation in mice compromises islet cell proliferation during embryogenesis. The aim of our study was to investigate an impact of CTGF genetic variation on pancreatic beta-cell function and T2DM pathogenesis. We studied the effect of a common CTGF polymorphism rs9493150 on the risk of the T2DM development in three independent German cohorts. Specifically, the association between CTGF polymorphism and non-invasive markers of beta-cell area derived from oral glucose tolerance test was studied in subjects without diabetes. Neither in the Metabolic Syndrome Berlin Potsdam (MESYBEPO) study (n=1026) (OR=0.637, CI (0.387-1.050); p=0.077) nor in the European Prospective Investigation into Cancer and Nutrition-Potsdam (EPIC-Potsdam) (n=3049) cohort (RR=0.77 CI (0.49-1.20), p=0.249 for the recessive homozygote in general model), a significant association with increased diabetes risk was observed. The risk allele of rs9493150 had also no effect on markers of beta-cell area in the combined analysis of the MESYBEPO and Tübingen Family Study (n=1826). In conclusion, the polymorphism rs9493150 in the 5'-untranslated region of the CTGF gene has no association with T2DM risk and surrogate markers of beta-cell area.
- Published
- 2011
- Full Text
- View/download PDF
50. Role of the gut Peptide glucose-induced insulinomimetic Peptide in energy balance.
- Author
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Pfeiffer AF, Rudovich N, Weickert MO, and Isken F
- Subjects
- Animals, Eating physiology, Energy Metabolism genetics, Female, Gastric Inhibitory Polypeptide genetics, Gastric Inhibitory Polypeptide metabolism, Gastrointestinal Hormones metabolism, Gastrointestinal Hormones physiology, Homeostasis genetics, Homeostasis physiology, Humans, Insulin-Secreting Cells metabolism, Insulin-Secreting Cells physiology, Male, Mice, Energy Metabolism physiology, Gastric Inhibitory Polypeptide physiology
- Abstract
Glucose-induced insulinomimetic peptide (GIP) is a gut hormone produced by enteroendocrine K-cells in the intestinal mucosa in response to fat, glucose, and also protein. GIP releases insulin from the β cells of the pancreatic islets of Langerhans and therefore is an incretin hormone. GIP acts on a G-protein-coupled receptor that is widely distributed in the body including adipose tissue, stomach, brain, and others. Deletion of the GIP receptor (GIPR) renders mice resistant to weight gain induced by a high fat diet.We observed that weight gain induced by ovarectomy in female mice is prevented by GIPR deletion that is linked to reduced food intake and reduced hypothalamic expression of orectic neurotransmitters. Moreover, old male GIPR(-/-) mice placed on a high glycemic index diet maintained a high insulin sensitivity and were much more active than controls, which was not seen in young animals. Thus, GIP elicits central effects in response to nutrients that protect against obesity and insulin resistance. We then investigated the acute responses of humans to treatment with GIP over 4h in a dose mimicking postprandial plasma levels of about 100pmol/L. At basal glucose, GIP does not elicit insulin release. Fat biopsies taken before and after 4h of GIP treatment were analyzed for transcriptomic responses using Agilent whole human genome assays. There was a highly significant upregulation of an inflammatory expression pattern in a pathway analysis.
- Published
- 2010
- Full Text
- View/download PDF
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