Author: "Alain D. Baron" / Language: english - Searchworks@Jio Institute Digital Library Search Results

8 results on '"Alain D. Baron"'

1. Improved glycemic control with minimal systemic metformin exposure: Effects of Metformin Delayed-Release (Metformin DR) targeting the lower bowel over 16 weeks in a randomized trial in subjects with type 2 diabetes

Author: Thomas A. Bicsak, Brandon Walsh, Mark Fineman, Juan P. Frias, Sharon Skare, Colleen Burns, John Hemming, Alain D. Baron, and Robert R. Henry
Subjects: Blood Glucose, Male, endocrine system diseases, lcsh:Medicine, Type 2 diabetes, 030204 cardiovascular system & hematology, Pathology and Laboratory Medicine, Biochemistry, Gastroenterology, law.invention, Endocrinology, 0302 clinical medicine, Randomized controlled trial, law, Chronic Kidney Disease, Medicine and Health Sciences, Diabetes diagnosis and management, Diabetic Nephropathies, lcsh:Science, education.field_of_study, Multidisciplinary, Pharmaceutics, digestive, oral, and skin physiology, Nausea, Middle Aged, Metformin, Type 2 Diabetes, Nephrology, Research Design, Female, Research Article, medicine.drug, Diarrhea, medicine.medical_specialty, HbA1c, Clinical Research Design, Endocrine Disorders, Population, 030209 endocrinology & metabolism, Gastroenterology and Hepatology, Research and Analysis Methods, Placebo, 03 medical and health sciences, Signs and Symptoms, Double-Blind Method, Drug Therapy, Ileum, Internal medicine, Diabetes mellitus, Diabetes Mellitus, Renal Diseases, medicine, Humans, Hypoglycemic Agents, Hemoglobin, education, Adverse effect, Glycemic, Glycated Hemoglobin, Biology and life sciences, business.industry, lcsh:R, Proteins, nutritional and metabolic diseases, medicine.disease, Diagnostic medicine, Diabetes Mellitus, Type 2, Delayed-Action Preparations, Metabolic Disorders, lcsh:Q, Adverse Events, business
Abstract: Objective Metformin use is restricted in patients with renal impairment due to potential excess systemic accumulation. This study evaluated the glycemic effects and safety of metformin delayed-release (Metformin DR), which targets metformin delivery to the ileum to leverage its gut-based mechanisms of action while minimizing systemic exposure. Research designs and methods Participants (T2DM [HbA1c 7–10.5%], eGFR ≥60 mL/min/1.73m2, not taking metformin for ≥2 months) were randomized to QD placebo (PBO); QD Metformin DR 600, 900, 1200, or 1500 mg; or to single-blind BID Metformin immediate-release (IR) 1000 mg. The primary endpoint was change in HbA1c for Metformin DR vs. PBO at 16 weeks in the modified intent-to-treat (mITT) population (≥ 1 post-baseline HbA1c while on study drug), using a mixed-effects repeated measures model. Results 571 subjects were randomized (56 years, 53% male, 80% white; BMI 32.2±5.5 kg/m2; HbA1c 8.6±0.9%; 51% metformin naive); 542 were in the mITT population. Metformin DR 1200 and 1500 mg significantly reduced HbA1c (-0.49±0.13% and -0.62±0.12%, respectively, vs. PBO -0.06±0.13%; p
Published: 2018

2. Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials

Author: Mark Fineman, Alain D. Baron, Sharon Skare, John B. Buse, Ralph A. DeFronzo, Terri Kim, and Colleen Burns
Subjects: Adult, Blood Glucose, Male, 0301 basic medicine, Clinical care, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Population, 030209 endocrinology & metabolism, Type 2 diabetes, Pharmacology, Article, Clinical study, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Glucagon-Like Peptide 1, Mechanisms, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Peptide YY, education, education.field_of_study, Cross-Over Studies, business.industry, digestive, oral, and skin physiology, nutritional and metabolic diseases, Fasting, Middle Aged, Postprandial Period, medicine.disease, Crossover study, Metformin, 030104 developmental biology, Postprandial, Tolerability, Pharmacodynamics, Lactate, Female, business, medicine.drug
Abstract: Aims/hypothesis Delayed-release metformin (Metformin DR) was developed to maximise gut-based mechanisms of metformin action by targeting the drug to the ileum. Metformin DR was evaluated in two studies. Study 1 compared the bioavailability and effects on circulating glucose and gut hormones (glucagon-like peptide-1, peptide YY) of Metformin DR dosed twice-daily to twice-daily immediate-release metformin (Metformin IR). Study 2 compared the bioavailability and glycaemic effects of Metformin DR dosages of 1,000 mg once-daily in the morning, 1,000 mg once-daily in the evening, and 500 mg twice-daily. Methods Study 1 was a blinded, randomised, crossover study (three × 5 day treatment periods) of twice-daily 500 mg or 1,000 mg Metformin DR vs twice-daily 1,000 mg Metformin IR in 24 participants with type 2 diabetes conducted at two study sites (Celerion Inc.; Tempe, AZ, and Lincoln, NE, USA). Plasma glucose and gut hormones were assessed over 10.25 h at the start and end of each treatment period; plasma metformin was measured over 11 h at the end of each treatment period. Study 2 was a non-blinded, randomised, crossover study (three × 7 day treatment periods) of 1,000 mg Metformin DR once-daily in the morning, 1,000 mg Metformin DR once-daily in the evening, or 500 mg Metformin DR twice-daily in 26 participants with type 2 diabetes performed at a single study site (Celerion, Tempe, AZ). Plasma glucose was assessed over 24 h at the start and end of each treatment period, and plasma metformin was measured over 30 h at the end of each treatment period. Both studies implemented centrally generated computer-based randomisation using a 1:1:1 allocation ratio. Results A total of 24 randomised participants were included in study 1; of these, 19 completed the study and were included in the evaluable population. In the evaluable population, all treatments produced similar significant reductions in fasting glucose (median reduction range, −0.67 to −0.81 mmol/l across treatments) and postprandial glucose (Day 5 to baseline AUC0–t ratio = 0.9 for all three treatments) and increases in gut hormones (Day 5 to baseline AUC0–t ratio range: 1.6–1.9 for GLP-1 and 1.4–1.5 for PYY) despite an almost 60% reduction in systemic metformin exposure for 500 mg Metformin DR compared with Metformin IR. A total of 26 randomised participants were included in study 2: 24 had at least one dose of study medication and at least one post-dose pharmacokinetic/pharmacodynamic assessment and were included in the pharmacokinetic/pharmacodynamic intent-to-treat analysis; and 12 completed all treatment periods and were included in the evaluable population. In the evaluable population, Metformin DR administered once-daily in the morning had 28% (90% CI −16%, −39%) lower bioavailability (least squares mean ratio of metformin AUC0–24) compared with either once-daily in the evening or twice-daily, although the glucose-lowering effects were maintained. In both studies, adverse events were primarily gastrointestinal in nature, and indicated similar or improved tolerability for Metformin DR vs Metformin IR; there were no clinically meaningful differences in vital signs, physical examinations or laboratory values. Conclusions/interpretation Dissociation of gut hormone release and glucose lowering from plasma metformin exposure provides strong supportive evidence for a distal small intestine-mediated mechanism of action. Directly targeting the ileum with Metformin DR once-daily in the morning may provide maximal metformin efficacy with lower doses and substantially reduce plasma exposure. Metformin DR may minimise the risk of lactic acidosis in those at increased risk from metformin therapy, such as individuals with renal impairment. Trial registration: Clinicaltrials.gov NCT01677299, NCT01804842 Funding: This study was funded by Elcelyx Therapeutics Inc. Electronic supplementary material The online version of this article (doi:10.1007/s00125-016-3992-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Published: 2016
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3. 40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004

Author: 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. Obrosova, J Fruchart, M Ilic, Björn Eliasson, Gilles Chatellier, M A Martín, D M Kendall, Holger Luthman, V F Varillas, D Maccubbin, Jang S-A., Amalia Gastaldelli, E Salzsieder, P. de Mol, A Yoshida, H D Lindner, D Gostiljac, M Just, Pan C-Y., J M Fujitaki, G Eiermann, K Bergenheim, A D Frick, A Agacdiken, K Varytimiadis, K Cseh, D A Jackson, S Calderari, Dena G. Hernandez, H M Liebich, K Min, F. de Zegher, Bernd Kulzer, K Han, Ulrich A. Müller, D Marrero, H Hatakeyama, René Koopman, Doo H-K., Petr Wohl, P. Sharp, P Forder, Thor Aspelund, N Meneveau, R M Schmülling, R Aubert, Thom Sam., H Youshikawa, M Ankelo, D Bowden, I Kelly, Frédéric Fumeron, M Sartini, Robert S. Sherwin, L Varadhan, A Criscimanna, John Betteridge, V Jelic, M Bartnik, N Lemke, B Ursø, A Bertoldo, A M Owona, H Okochi, L Pérez-Tamajó, S L Monfre, Daniel Brandhorst, K T Legg, Andries J. Smit, Veronica Sancho, Masashi Hirai, C Klein, Paul J. Thornalley, A Chaidaroglou, K Miura, B Zinman, O M Dvoynishnikova, J Plank, Jan Bolinder, C Lush, B Rubi, R Pozzilli, M Bashir, S A Shtandel, F Mosca, A Naskalska, Josef Vcelak, U Sausbier, P Cavaiani, T U Baehring, Michele Solimena, P Formisano, M Rastaldi, Bernard Thorens, J Ruzzin, E Arbit, M. Hori, Torkel B. Brismar, E Soltes Rak, A Filo, P Heinke, Matthew P. Coghlan, M Masotti, I Perevozskaya, K Ahn, I Moules, K Van Dyck, I Goldstein, Z Mathe, G Z Zhao, S Fajardo, J Taylor, S Chrul, J C Pareja, D Hadjidakis, A J Scheen, N Siddiqua, D C Cavan, R Grella, Krabbe S, H J Rochlitz, A E Hinkkanen, W Wilpshaar, Richard Stevens, M Dreyer, S Hara, X Wang, Melania Manco, D Gillen, Magalie A. Ravier, Olli Simell, John C. Lawrence, Kohnert K-D., Agardh C-D., A Berghold, L Kristensen, Grant Sfa., N Gursoy, Leif Groop, N Freemantle, Anja Schweizer, L Pala, Legros J-J., C. Di Pietro, N. Yamamoto, J Magyar, B Nikolovski, H Ikeda, D Lee, Bruce A. Buckingham, A O Wollitzer, I Kennedy, C Ernest, Neville H. McClenaghan, S Tanaka, Asimina Mitrakou, T Heinze, W Kerner, Moeenaldeen Al-Sayed, Charles Thivolet, L Klaff, A Miconi, Cristina Valeri, J. O. Christensen, K. Ekberg, A Jardine, T Endo, X Zhang, D F Child, A Kienitz, D K Seidel, H. Tada, Sylvie Abouna, Cyrus Cooper, Catherine R Chittleborough, Roberta Assaloni, S Corbi, A K Bose, K Ozawa, C Ahn, K A Deans, G Jackowski, Martin Gibson, Patrick McElduff, O A Mojiminiyi, Manuel Serrano-Ríos, O Dupuy, A L Davydov, Iwar Klimes, Sten-Anders Ivarsson, N Ichino, R Matsutomo, E R Smith, A Stefanovska, B Dehmel, K Koniavitou, E Agascioglu, M Hatazaki, J. M. Gibson, T Yada, P Ribaux, M Rupnik, K Fridell, G Scutaru, L Chugunova, Henrietta Mulnier, A Kendereski, H Lehnert, C Billi, M Sobczak, Francisco M-Mj., L K Archibald, S Sukumvanich, David B. Dunger, I. Benke, G Yillar, N Stingemore, J. M. Boavida, Y Shi, Jimmy D. Bell, L Bozzetto, Andrew J. Ahmann, E Jebens, J Keiding, Elena Henkel, Mark Fineman, J F McRae, Carol Forsblom, S Martemucci, Lourdes Ibáñez, P G Prieto, L Ringholm Nielsen, S Pratas, B von Stritzky, Julio Rosenstock, Lee K-W., J Stocks, L J Strow, I Samarguliani, L Wennekes, R Cheung, Abhishek Nag, Roberto Gambino, Y Suleymanoglu, E Murphy, T T Durck, M F Peyrot, Y Unno, Alexander Mayorov, Eleuterio Ferrannini, D. C. Rao, D Neely, H Karunajeewa, J Palmisano, Julia B. Lewis, M Ravid, G Pons, E Junca, P Vexiau, S Sailesh, D K Miloslavskiy, O N Bondarenko, U Smith, S Torri, Constantine Tsigos, Cesario Bianchi, Mattia Locatelli, D Jaquet, Virpi Lindi, M Moroi, M E Tushuizen, P Pelicci, R Scognamiglio, Pal Pacher, S M Thyssen, A Péterfalvi, Y Ho, S Guntram, L Romics, T Nakagami, Clive S. Cockram, Irina Kowalska, K Brodbeck, Gojka Roglic, J. Dörig, Lise Tarnow, Therese Tillin, A López-Alba, Martin Krššák, Moses Elisaf, S Hata, D P Snoeck, D Schmoll, O V Udovichenko, A Scaramuzza, J Paul, John H. 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Lyu, G Rizzo, V V Bogomolov, N Krasova, G M McGuire, Tina Parkner, A Timi, Johann Bauersachs, S Foussas, S A Schreiber, T Monauni, Schwarz Peh., Allenberg, J D Lee, S Dewan, Y G Zheng, D Carroll, E Sarti, C Wollheim, Anna Kaminski, C Menneila, P Bucher, Xu Jyu., Vincent Rigalleau, A Schöpfer, Hans Jörnvall, A Ben Drief, X Jeunemaitre, E Schuster, Chan Slf., S Bilgic, J Coverly, K Szafraniec, Stalenhoef Afh., H Bergert, David I. W. Phillips, J Maksimovic Pavlovic, Sergio E. Starkstein, E Chaim, T Lehmann-Lintz, P Salacone, Tim Armstrong, Ingrid Klöting, C M Frampton, Franco Cavalot, A.K.Azad Khan, H Rose, Marta Letizia Hribal, Jette Kolding Kristensen, H Gröbe, M Nishi, A Vanderplas, Howlett Hsc., L E Bowen, R Malik, A Wu, Charles C. Richardson, Y Li, P G McNally, Yoon K-H., A Baleydier, M J Murphy, P. M. Nilsson, U Lindblad, Sten Madsbad, T Bíró, Riitta Veijola, Charlotte Glümer, Assunta Pandolfi, Lydia Aguilar-Bryan, M Namba, C Franzen, S Lopatriello, David Russel Jones, S. 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Jeffcoate, J Pariès, K Huoponen, Anne Jörns, G Shanmugam, A Tsiavou, S Yoshida, Kim M-J., Annapaula Giulietti, S Paillasson, K Tsuchiya, Divyen K Shah, P Saar, S S Juarez, Stefanie Maxion-Bergemann, J Briody, V Schmitz, C M Pena, J Fernádez-Real, S Naruse, M Kalis, A P Klimenko, X H Chen, H.H. Lervang, G Bock, Mirja Tiikkainen, J Potockova, N Pekcanli, George Dragicevic, Timothy M. Rose, David C. Goff, H Komori, V Vasseur-Delannoy, S Hanley, P Hajos, C W Ahn, Matsuoka T-A., J Burns, Petar M. Seferovic, Yuki Kita, K Lyons, K Kohri, Eleftheria Zeggini, Y Ding, G Belcher, Steven V. Edelman, N Dinççaǧ, Christopher J. Rhodes, Manders Rjf., S Giveon, Dario Iafusco, L Li, M C Ribaudo, Kang S-K., Laurie J. Goodyear, L Martinez, C Vermigli, H Dabire, R Raymond, J de Haan, Christopher J. Groves, Å Norberg, H Jahr, M Gloster, Christopher D. 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Leon, Alberti Gkm., A Opel, S Kokkoris, S B Hong, Philippe Courtois, L Haque, Maria Sörhede Winzell, M C Beauvois, A Szypowska, D Yu, M Gutniak, D Petzinna, B Isomaa, K S Prickett, Maria Felice Brizzi, Pavel Hamet, P J Hammond, K. F. Michelmore, Yumie Takeshita, N Hariharan, Corrado M. Cilio, G Pogatsa, W G Jerome, E Bartley, K Schlembacher, G Blohmó, Guy A. Rutter, Kyung Mook Choi, S. C Tamer, Felix K. Assah, K A Jandeleit-Dahm, M Chan, H Darius, Jørgen F. P. Wojtaszewski, A Papazisi, M Amaya, A Knopff, M Tadayyon, I J Kim, W Russ, T Myrnäs, M. Tryon, S Poonsatha, Noel Cameron, Kim M-H., Alejandra Tomas, F Homo-Dekarche, G. Di Cianni, M Stotzka, C Solimine, Mikhail Borisovich Antsiferov, H Naserke, M Bianchi-Biscay, J I Lara, Moon C-K., Alain Ktorza, Alison N. Jeffery, V Lilla, Eun Seok Kang, Hanley Ajg., J Widder, R Ratner, C Goretti, P J Weston, J Perkins, V Rasmussen, M Evans, T M Gibson, A Jaffe, S I Chisalita, C Owman, L Hiltunen, E Kakishita, C M Mack, H C Potter, M Femerling, M Desai, M Soinio, K Yang, Patricia L. Brubaker, M Meyer, V Dy, J Berden, R Komers, Milos Adamec, R Petzoldt, Alan G. Robinson, R Stevens, A Doi, A Leunda, Eduard Montanya, Alessandra K Cardozo, N Kraenkel, Claudio Cobelli, U A Mueller, S Yamashiro, B R Gedulin, G Francisco, J Dennenmoser, Lesch K-P., Martin G. Bischof, M Ichita, C Fernandes, Jochen Hampe, S Kern, D Kelly, E Zeender, P Perna, J D Best, A C Calkin, Vivian Fonseca, J Prestle, D G Parkes, Satish K. Garg, T Burrell, B M Fischer, D Kruger, J S Skinner, Lin T-M., Jozef Ukropec, Maria Jeziorska, K Arii, David D. D’Alessio, M B Gomes, L Quandt, I Fragaki, M C Brindisi, A Gladkih, E Kitsou, S Di Cola, T Iwasaki, Peter Diem, T Lakka, V V Popova, G Lee, Hannah J. 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Cavanagh, Allen Taylor, M Balabolkin, G Schreier, E Stern, J Lips, V Serban, G Sparacino, Roser Casamitjana, Aine McKillop, I Groza, E Bernal, Kathleen M Gillespie, T Ledet, A Garzaniti, F Hawkins, K M Tushaus, C Renaudin, Christina Maier, A Dormi, A Ubertalli, Inge Tetens, M Ostojic, E Pierre-Justin, A Bhushan, E Ur, L I Jeltova, Tilo Moede, E Tibiriça, Zoran Gucev, Knoch K-P., G Pizzolanti, A M Şengül, T P Degenhardt, Cristina Lencioni, M Fitchet, E Santini, E Devangelio, C Panaite, Y I Karachentsev, S B Solerte, Christos Manes, M Lipka, C H Teng, P Mrak, G Fegan, R C Milton, M Negrean, Astrid Plamboeck, L Patti, M Houk, Ritva Kauppinen-Mäkelin, Christoph F Ebenbichler, O Sysoyeva, Frantisek Saudek, H Wysocki, Robert A. Rizza, J Altirriba, Bjørn Richelsen, L. Lam, Rémy Burcelin, A Antsaklis, G Galimberti, R. de Vries, A Lewin, Marcia A. 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Vingrys, S Habu, Mariella Trovati, H Sobajima, Pierre Lecomte, Kim T-H., D Virsaladze, M Oprean, F Pullen, A Rußmann, G J Bruining, Martina Düfer, Wen Xu, Min Y-K., Norman E Cameron, Gianfranco Pagano, K Harley, M Su, J P Le Berre, Sian Ellard, S Howard, D Russell-Jones, Z Li, S Carpenter, E L Thomas, W Tang, Lee M-S., N Ubrich, M. M. McMahon, G Vassilikos, N Brossa, M S Joergensen, S Smith, A Vania, Y Laurent, S Basir, A Freudenthaler, Sally M. Marshall, D Niedermayer, V I Pankiv, J Mentel, S Pruna, J M Pou Torelló, Y Ito, G Chrysos, Werner Kramer, Hironori Yamasaki, L Bowman, F Palumbo, P Ruth, G Lankas, Z H Liao, D Park, W Otter, C Montrone, Sevasti Zervou, Jennifer L. Wilkinson-Berka, Bo Feldt-Rasmussen, I Banu, Paolo Sbraccia, Bani Mukhopadhyay, Mark E. Cooper, M Kidron, Pål R. Njølstad, A M Jonsdottir, M R Burge, G Valpiani, Yutaka Oiso, David J. 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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
Subjects: 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

4. Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle. Implications for glucose toxicity

Author: L. Maianu, Alain D. Baron, H. Weldon, Ju-Hong Zhu, W T Garvey, and Jin-Su Zhu
Subjects: Blood Glucose, Male, medicine.medical_specialty, Time Factors, Monosaccharide Transport Proteins, Glucose uptake, medicine.medical_treatment, Phospholemman, Muscle Proteins, Biology, Carbohydrate metabolism, Rats, Sprague-Dawley, Insulin resistance, Internal medicine, Hyperinsulinism, medicine, Animals, Insulin, Infusions, Intravenous, Muscle, Skeletal, Glucosamine, Glucose Transporter Type 4, Dose-Response Relationship, Drug, Cell Membrane, Glucose transporter, General Medicine, Glucose clamp technique, medicine.disease, Rats, Kinetics, Endocrinology, Glucose, Glucose Clamp Technique, Insulin Resistance, Research Article
Abstract: Glucosamine (Glmn), a product of glucose metabolism via the hexosamine pathway, causes insulin resistance in isolated adipocytes by impairing insulin-induced GLUT 4 glucose transporter translocation to the plasma membrane. We hypothesized that Glmn causes insulin resistance in vivo by a similar mechanism in skeletal muscle. We performed euglycemic hyperinsulinemic clamps (12 mU/kg/min + 3H-3-glucose) in awake male Sprague-Dawley rats with and without Glmn infusion at rates ranging from 0.1 to 6.5 mg/kg/min. After 4h of euglycemic clamping, hindquarter muscles were quick-frozen and homogenized, and membranes were subfractionated by differential centrifugation and separated on a discontinuous sucrose gradient (25, 30, and 35% sucrose). Membrane proteins were solubilized and immunoblotted for GLUT 4. With Glmn, glucose uptake (GU) was maximally reduced by 33 +/- 1%, P < 0.001. The apparent Glmn dose to reduce maximal GU by 50% was 0.1 mg/kg/min or 1/70th the rate of GU on a molar basis. Control galactosamine and mannosamine infusions had no effect on GU. Relative to baseline, insulin caused a 2.6-fold increase in GLUT 4 in the 25% membrane fraction (f), P < 0.01, and a 40% reduction in the 35%f, P < 0.05, but had no effect on GLUT 4 in the 30% f, P= NS. Addition of Glmn to insulin caused a 41% reduction of GLUT 4 in the 25%f, P < 0.05, a 29% fall in the 30%f, and prevented the reduction of GLUT 4 in the 35% f. The 30%f membranes were subjected to a second separation with a 27 and 30% sucrose gradient. Insulin mobilized GLUT 4 away from the 30%f, P < 0.05, but not the 27% f. In contrast, Glmn reduced GLUT 4 in the 27%f, P < 0.05, but not the 30%f. Thus Glmn appears to alter translocation of an insulin-insensitive GLUT 4 pool. Coinfusion of Glmn did not alter enrichment of the sarcolemmal markers 5'-nucleotidase, Na+/K+ATPase, and phospholemman in either 25, 30, or 35% f. Thus Glmn completely blocked movement of Glut 4 induced by insulin. Glmn is a potent inducer of insulin resistance in vivo by causing (at least in part) a defect intrinsic to GLUT 4 translocation and/or trafficking. These data support a potential role for Glmn to cause glucose-induced insulin resistance (glucose toxicity).
Published: 1995

5. Insulin-mediated skeletal muscle vasodilation contributes to both insulin sensitivity and responsiveness in lean humans

Author: Alain D. Baron, Ginger Brechtel, H Chaker, Rosalind Leaming, Helmut O. Steinberg, and Ann Johnson
Subjects: Adult, medicine.medical_specialty, Glucose uptake, medicine.medical_treatment, Vasodilation, Carbohydrate metabolism, Arginine, Body Mass Index, Insulin resistance, Internal medicine, medicine, Hyperinsulinemia, Humans, Insulin, Hindsight, Muscle, Skeletal, Leg, omega-N-Methylarginine, business.industry, General Medicine, Fasting, Glucose clamp technique, medicine.disease, Endocrinology, Glucose, Basal (medicine), Regional Blood Flow, Body Composition, Glucose Clamp Technique, Insulin Resistance, business, Research Article
Abstract: Whether insulin-mediated vasodilation is important in determining insulin's overall action to stimulate glucose uptake is unknown. To this end, we measured leg glucose uptake during euglycemic hyperinsulinemic clamps performed at two insulin doses (40 mU/m2 per min, n = 6 and 120 mU/m2 per min, n = 15) alone and during a superimposed intrafemoral artery infusion of GN-monomethyl-L-arginine (L-NMMA) designed to blunt insulin-mediated vasodilation. During the higher dose study, hyperinsulinemia resulted in about a twofold rise in basal leg blood flow from 0.24 +/- 0.02 to 0.45 +/- 0.05 liter/min, P < 0.0001. L-NMMA infusion resulted in a net 21% reduction in leg glucose uptake from 114 +/- 18 mg/min to 85 +/- 13 mg/min, P < 0.001. We also found a significant relationship between the rate of insulin-stimulated whole body glucose uptake and the magnitude of flow dependent glucose uptake (r = 0.57, P = 0.02). Data obtained during the lower dose insulin infusion resulted in similar findings. In conclusion, in healthy lean subjects, insulin-stimulated muscle blood flow contributes to both insulin responsiveness and insulin sensitivity. The most insulin-sensitive subjects appear to be the most reliant on muscle perfusion for insulin action. Insulin-mediated vasodilation is an important physiological determinant of insulin action.
Published: 1995

6. Reduced capacity and affinity of skeletal muscle for insulin-mediated glucose uptake in noninsulin-dependent diabetic subjects. Effects of insulin therapy

Author: Steven V. Edelman, Alain D. Baron, Ginger Brechtel, and Markku Laakso
Subjects: Blood Glucose, Male, medicine.medical_specialty, Glucose uptake, medicine.medical_treatment, Carbohydrate metabolism, Insulin resistance, Internal medicine, Diabetes mellitus, medicine, Humans, Insulin, Obesity, Glycemic, Glycated Hemoglobin, Leg, business.industry, Muscles, Skeletal muscle, Biological Transport, General Medicine, medicine.disease, medicine.anatomical_structure, Endocrinology, Glucose, Diabetes Mellitus, Type 2, Arterial blood, business, Blood Flow Velocity, Research Article
Abstract: We have estimated the capacity and affinity of insulin-mediated glucose uptake (IMGU) in whole body and in leg muscle of obese non-insulin-dependent diabetics (NIDDM, n = 6) with severe hyperglycemia, glycohemoglobin (GHb 14.4 +/- 1.2%), lean controls (ln, n = 7) and obese nondiabetic controls (ob, n = 7). Mean +/- SEM weight (kg) was 67 +/- 2 (ln), 100 +/- 7 (ob), and 114 +/- 11 (NIDDM), P = NS between obese groups. NIDDM were also studied after 3 wk of intensive insulin therapy, GHb post therapy was 10.1 +/- 0.9, P less than 0.01 vs. pretherapy. Insulin (120 mu/m2 per min) was infused and the arterial blood glucose (G) sequentially maintained at approximately 4, 7, 12, and 21 mmol/liter utilizing the G clamp technique. Leg glucose uptake (LGU) was calculated as the product of the femoral arteriovenous glucose difference (FAVGd) and leg blood flow measured by thermodilution. Compared to ln, ob and NIDDM had significantly lower rates of whole body IMGU and LGU at all G levels. Compared to ob, the NIDDM exhibited approximately 50% and approximately 40% lower rates of whole body IMGU over the first two G levels (P less than 0.02) but did not differ at the highest G, P = NS. LGU was 83% lower in NIDDM vs. ob, P less than 0.05 at the first G level only. After insulin therapy NIDDM were indistinguishable from ob with respect to whole body IMGU or LGU at all G levels. A significant correlation was noted between the percent GHb and the EG50 (G at which 1/2 maximal FAVGd occurs) r = 0.73, P less than 0.05. Thus, (a) insulin resistance in NIDDM and obese subjects are characterized by similar decreases in capacity for skeletal muscle IMGU, but differs in that poorly controlled NIDDM display a decrease in affinity for skeletal muscle IMGU, and (b) this affinity defect is related to the degree of antecedent glycemic control and is reversible with insulin therapy, suggesting that it is an acquired defect.
Published: 1991

7. Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance

Author: Alain D. Baron, Steven V. Edelman, Ginger Brechtel, and M Laakso
Subjects: Adult, medicine.medical_specialty, Glucose uptake, medicine.medical_treatment, Hemodynamics, Biology, Carbohydrate metabolism, Fatty Acids, Nonesterified, Insulin resistance, Internal medicine, medicine, Humans, Insulin, Obesity, Leg, Muscles, Skeletal muscle, Biological Transport, General Medicine, Blood flow, medicine.disease, Endocrinology, medicine.anatomical_structure, Glucose, Basal (medicine), Regional Blood Flow, Lactates, Regression Analysis, Insulin Resistance, Research Article
Abstract: Obesity is characterized by decreased rates of skeletal muscle insulin-mediated glucose uptake (IMGU). Since IMGU equals the product of the arteriovenous glucose difference (AVGd) across muscle and blood flow into muscle, reduced blood flow and/or tissue activity (AVGd) can lead to decreased IMGU. To examine this issue, we studied six lean (weight 68 +/- 3 kg, mean +/- SEM) and six obese (94 +/- 3 kg) men. The insulin dose-response curves for whole body and leg IMGU were constructed using the euglycemic clamp and leg balance techniques over a large range of serum insulin concentrations. In lean and obese subjects, whole body IMGU, AVGd, blood flow, and leg IMGU increased in a dose dependent fashion and maximal rates of all parameters were reduced in obese subjects compared to lean subjects. The dose-response curves for whole body IMGU, leg IMGU, and AVGd were right-shifted in obese subjects with an ED50 two- to threefold higher than that of lean subjects for each parameter. Leg blood flow increased approximately twofold from basal 2.7 +/- 0.2 to 4.4 +/- 0.2 dl/min in lean, P less than 0.01, and from 2.5 +/- 0.3 to 4.4 +/- 0.4 dl/min in obese subjects, P less than 0.01. The ED50 for insulin's effect to increase leg blood flow was about fourfold higher for obese (957 pmol/liter) than lean subjects (266 pmol/liter), P less than 0.01. Therefore, decreased insulin sensitivity in human obesity is not only due to lower glucose extraction in insulin-sensitive tissues but also to lower blood flow to these tissues. Thus, in vivo insulin resistance can be due to a defect in insulin action at the tissue level and/or a defect in insulin's hemodynamic action to increase blood flow to insulin sensitive tissues.
Published: 1990

8. Glucagon-like peptide-1 and the exenatide analogue AC3174 improve cardiac function, cardiac remodeling, and survival in rats with chronic heart failure

Author: Alain D. Baron, David G. Parkes, Christen M. Anderson, Anatoly Broyde, Clara Polizzi, Que Liu, and Rayne Fernandez
Subjects: Blood Glucose, Male, Cardiac function curve, medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, Cardiotonic Agents, Time Factors, Endocrinology, Diabetes and Metabolism, Myocardial Infarction, Diastole, Infusions, Subcutaneous, Ventricular Function, Left, Rats, Sprague-Dawley, Glucagon-Like Peptide 1, Internal medicine, Ventricular Pressure, medicine, Animals, Insulin, Myocardial infarction, Ventricular remodeling, Original Investigation, Echocardiography, Doppler, Pulsed, Heart Failure, Glucose Transporter Type 1, Exercise Tolerance, Glucose Transporter Type 4, Ejection fraction, Ventricular Remodeling, business.industry, Myocardium, Hemodynamics, Stroke Volume, Stroke volume, medicine.disease, Rats, Disease Models, Animal, Endocrinology, lcsh:RC666-701, Heart failure, Chronic Disease, Cardiology, End-diastolic volume, Peptides, business, Cardiology and Cardiovascular Medicine
Abstract: Background Accumulating evidence suggests glucagon-like peptide-1 (GLP-1) exerts cardioprotective effects in animal models of myocardial infarction (MI). We hypothesized that chronic treatment with GLP-1 or the exenatide analog AC3174 would improve cardiac function, cardiac remodeling, insulin sensitivity, and exercise capacity (EC) in rats with MI-induced chronic heart failure (CHF) caused by coronary artery ligation. Methods Two weeks post-MI, male Sprague-Dawley rats were treated with GLP-1 (2.5 or 25 pmol/kg/min), AC3174 (1.7 or 5 pmol/kg/min) or vehicle via subcutaneous infusion for 11 weeks. Cardiac function and morphology were assessed by echocardiography during treatment. Metabolic, hemodynamic, exercise-capacity, and body composition measurements were made at study end. Results Compared with vehicle-treated rats with CHF, GLP-1 or AC3174 significantly improved cardiac function, including left ventricular (LV) ejection fraction, and end diastolic pressure. Cardiac dimensions also improved as evidenced by reduced LV end diastolic and systolic volumes and reduced left atrial volume. Vehicle-treated CHF rats exhibited fasting hyperglycemia and hyperinsulinemia. In contrast, GLP-1 or AC3174 normalized fasting plasma insulin and glucose levels. GLP-1 or AC3174 also significantly reduced body fat and fluid mass and improved exercise capacity and respiratory efficiency. Four of 16 vehicle control CHF rats died during the study compared with 1 of 44 rats treated with GLP-1 or AC3174. The cellular mechanism by which GLP-1 or AC3174 exert cardioprotective effects appears unrelated to changes in GLUT1 or GLUT4 translocation or expression. Conclusions Chronic treatment with either GLP-1 or AC3174 showed promising cardioprotective effects in a rat model of CHF. Hence, GLP-1 receptor agonists may represent a novel approach for the treatment of patients with CHF or cardiovascular disease associated with type 2 diabetes.
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8 results on '"Alain D. Baron"'

1. Improved glycemic control with minimal systemic metformin exposure: Effects of Metformin Delayed-Release (Metformin DR) targeting the lower bowel over 16 weeks in a randomized trial in subjects with type 2 diabetes

2. Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials

3. 40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004

4. Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle. Implications for glucose toxicity

5. Insulin-mediated skeletal muscle vasodilation contributes to both insulin sensitivity and responsiveness in lean humans

6. Reduced capacity and affinity of skeletal muscle for insulin-mediated glucose uptake in noninsulin-dependent diabetic subjects. Effects of insulin therapy

7. Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance

8. Glucagon-like peptide-1 and the exenatide analogue AC3174 improve cardiac function, cardiac remodeling, and survival in rats with chronic heart failure

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