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1. Bidirectional modulation of TCA cycle metabolites and anaplerosis by metformin and its combination with SGLT2i

Author

Harada, Makoto, Adam, Jonathan, Covic, Marcela, Ge, Jianhong, Brandmaier, Stefan, Muschet, Caroline, Huang, Jialing, Han, Siyu, Rommel, Martina, Rotter, Markus, Heier, Margit, Mohney, Robert P., Krumsiek, Jan, Kastenmüller, Gabi, Rathmann, Wolfgang, Zou, Zhongmei, Zukunft, Sven, Scheerer, Markus F., Neschen, Susanne, Adamski, Jerzy, Gieger, Christian, Peters, Annette, Ankerst, Donna P., Meitinger, Thomas, Alderete, Tanya L., de Angelis, Martin Hrabe, Suhre, Karsten, and Wang-Sattler, Rui

Published
2024
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4. N-acyl Taurines and Acylcarnitines Cause an Imbalance in Insulin Synthesis and Secretion Provoking β Cell Dysfunction in Type 2 Diabetes

Author

Aichler, Michaela, Borgmann, Daniela, Krumsiek, Jan, Buck, Achim, MacDonald, Patrick E., Fox, Jocelyn E. Manning, Lyon, James, Light, Peter E., Keipert, Susanne, Jastroch, Martin, Feuchtinger, Annette, Mueller, Nikola S., Sun, Na, Palmer, Andrew, Alexandrov, Theodore, Hrabe de Angelis, Martin, Neschen, Susanne, Tschöp, Matthias H., and Walch, Axel

Published
2017
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8. Mouse Genetics and Metabolic Mouse Phenotyping

Author

Fuchs, Helmut, Neschen, Susanne, Rozman, Jan, Rathkolb, Birgit, Wagner, Sibylle, Adler, Thure, Afonso, Luciana, Aguilar-Pimentel, Juan Antonio, Becker, Lore, Bohla, Alexander, Calzada-Wack, Julia, Cohrs, Christian, Frankó, András, Garrett, Lillian, Glasl, Lisa, Götz, Alexander, Hagn, Michael, Hans, Wolfgang, Hölter, Sabine M., Horsch, Marion, Kahle, Melanie, Kistler, Martin, Klein-Rodewald, Tanja, Lengger, Christoph, Ludwig, Tonia, Maier, Holger, Marschall, Susan, Micklich, Kateryna, Möller, Gabriele, Naton, Beatrix, Neff, Frauke, Prehn, Cornelia, Puk, Oliver, Rácz, Ildikó, Räß, Michael, Scheerer, Markus, Schiller, Evelyn, Schöfer, Felix, Schrewe, Anja, Steinkamp, Ralph, Stöger, Claudia, Treise, Irina, Willershäuser, Monja, Wolff-Muscate, Annemarie, Zeh, Ramona, Adamski, Jerzy, Beckers, Johannes, Bekeredjian, Raffi, Busch, Dirk H., Favor, Jack, Graw, Jochen, Katus, Hugo, Klopstock, Thomas, Ollert, Markus, Schulz, Holger, Stöger, Tobias, Wurst, Wolfgang, Yildirim, Ali Önder, Zimmer, Andreas, Wolf, Eckhard, Klingenspor, Martin, Gailus-Durner, Valérie, de Angelis, Martin Hrabě, and Suhre, Karsten, editor

Published
2012
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9. The German Mouse Clinic – Running an Open Access Platform

Author

Gailus-Durner, Valérie, Naton, Beatrix, Adler, Thure, Afonso, Luciana, Aguilar-Pimentel, Juan Antonio, Becker, Lore, Calzada-Wack, Julia, Cohrs, Christian, da Silva-Buttkus, Patricia, Hans, Wolfgang, Horsch, Marion, Kahle, Melanie, Lengger, Christoph, Ludwig, Tonia, Maier, Holger, Micklich, Kateryna, Möller, Gabriele, Neff, Frauke, Neschen, Susanne, Prehn, Cornelia, Rathkolb, Birgit, Rozman, Jan, Schiller, Evelyn, Schrewe, Anja, Scheerer, Markus, Schöfer, Felix, Steinkamp, Ralph, Stöger, Claudia, Thiele, Frank, Tost, Monica, Treise, Irina, Willershäuser, Monja, Zeh, Ramona, Adamski, Jerzy, Bekeredjian, Raffi, Beckers, Johannes, Esposito, Irene, Höfler, Heinz, Katus, Hugo, Klingenspor, Martin, Klopstock, Thomas, Ollert, Markus, Wolf, Eckhard, Busch, Dirk H., Fuchs, Helmut, Hrabě de Angelis, Martin, Brakebusch, Cord, editor, and Pihlajaniemi, Taina, editor

Published
2011
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11. Acute dietary fat intake initiates alterations in energy metabolism and insulin resistance

Author

Hernandez, Elisa Alvarez, Kahl, Sabine, Seelig, Anett, Begovatz, Paul, Irmler, Martin, Kupriyanova, Yuliya, Nowotny, Bettina, Nowotny, Peter, Herder, Christian, Barosa, Cristina, Carvalho, Filipa, Rozman, Jan, Neschen, Susanne, Jones, John G., Beckers, Johannes, de Angelis, Martin Hrabe, and Roden, Michael

Subjects
Development and progression, Health aspects, Energy metabolism -- Health aspects, High fat diet -- Health aspects, Insulin resistance -- Development and progression, Ketogenic diet -- Health aspects, Bioenergetics -- Health aspects
Abstract

Introduction The pandemic of obesity, type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) has frequently been associated with dietary intake of saturated fats (1) and specifically with [...], BACKGROUND. Dietary intake of saturated fat is a likely contributor to nonalcoholic fatty liver disease (NAFLD) and insulin resistance, but the mechanisms that initiate these abnormalities in humans remain unclear. We examined the effects of a single oral saturated fat load on insulin sensitivity, hepatic glucose metabolism, and lipid metabolism in humans. Similarly, initiating mechanisms were examined after an equivalent challenge in mice. METHODS. Fourteen lean, healthy individuals randomly received either palm oil (PO) or vehicle (VCL). Hepatic metabolism was analyzed using in vivo [sup.13]C/[sup.31]P/¹H and ex vivo ²H magnetic resonance spectroscopy before and during hyperinsulinemiceuglycemic clamps with isotope dilution. Mice underwent identical clamp procedures and hepatic transcriptome analyses. RESULTS. PO administration decreased whole-body, hepatic, and adipose tissue insulin sensitivity by 25%, 15%, and 34%, respectively. Hepatic triglyceride and ATP content rose by 35% and 16%, respectively. Hepatic gluconeogenesis increased by 70%, and net glycogenolysis declined by 20%. Mouse transcriptomics revealed that PO differentially regulates predicted upstream regulators and pathways, including LPS, members of the TLR and PPAR families, NF-κB, and TNF-related weak inducer of apoptosis (TWEAK). CONCLUSION. Saturated fat ingestion rapidly increases hepatic lipid storage, energy metabolism, and insulin resistance. This is accompanied by regulation of hepatic gene expression and signaling that may contribute to development of NAFLD. REGISTRATION. ClinicalTrials.gov NCT01736202. FUNDING. Germany: Ministry of Innovation, Science, and Research North Rhine-Westfalia, German Federal Ministry of Health, Federal Ministry of Education and Research, German Center for Diabetes Research, German Research Foundation, and German Diabetes Association. Portugal: Portuguese Foundation for Science and Technology, FEDER--European Regional Development Fund, Portuguese Foundation for Science and Technology, and Rede Nacional de Ressonancia Magnetica Nuclear.

Published
2017
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13. Mouse phenotyping

Author

Fuchs, Helmut, Gailus-Durner, Valérie, Adler, Thure, Aguilar-Pimentel, Juan Antonio, Becker, Lore, Calzada-Wack, Julia, Da Silva-Buttkus, Patricia, Neff, Frauke, Götz, Alexander, Hans, Wolfgang, Hölter, Sabine M., Horsch, Marion, Kastenmüller, Gabi, Kemter, Elisabeth, Lengger, Christoph, Maier, Holger, Matloka, Mikolaj, Möller, Gabriele, Naton, Beatrix, Prehn, Cornelia, Puk, Oliver, Rácz, Ildikó, Rathkolb, Birgit, Römisch-Margl, Werner, Rozman, Jan, Wang-Sattler, Rui, Schrewe, Anja, Stöger, Claudia, Tost, Monica, Adamski, Jerzy, Aigner, Bernhard, Beckers, Johannes, Behrendt, Heidrun, Busch, Dirk H., Esposito, Irene, Graw, Jochen, Illig, Thomas, Ivandic, Boris, Klingenspor, Martin, Klopstock, Thomas, Kremmer, Elisabeth, Mempel, Martin, Neschen, Susanne, Ollert, Markus, Schulz, Holger, Suhre, Karsten, Wolf, Eckhard, Wurst, Wolfgang, Zimmer, Andreas, and Hrabě de Angelis, Martin

Published
2011
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15. Distinct signatures of host–microbial meta-metabolome and gut microbiome in two C57BL/6 strains under high-fat diet

Author

Walker, Alesia, Pfitzner, Barbara, Neschen, Susanne, Kahle, Melanie, Harir, Mourad, Lucio, Marianna, Moritz, Franco, Tziotis, Dimitrios, Witting, Michael, Rothballer, Michael, Engel, Marion, Schmid, Michael, Endesfelder, David, Klingenspor, Martin, Rattei, Thomas, Castell, Wolfgang zu, de Angelis, Martin Hrabé, Hartmann, Anton, and Schmitt-Kopplin, Philippe

Published
2014
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18. Innovations in phenotyping of mouse models in the German Mouse Clinic

Author

Fuchs, Helmut, Gailus-Durner, Valérie, Neschen, Susanne, Adler, Thure, Afonso, Luciana Caminha, Aguilar-Pimentel, Juan Antonio, Becker, Lore, Bohla, Alexander, Calzada-Wack, Julia, Cohrs, Christian, Dewert, Anna, Fridrich, Barbara, Garrett, Lillian, Glasl, Lisa, Götz, Alexander, Hans, Wolfgang, Hölter, Sabine M., Horsch, Marion, Hurt, Anja, Janas, Eva, Janik, Dirk, Kahle, Melanie, Kistler, Martin, Klein-Rodewald, Tanja, Lengger, Christoph, Ludwig, Tonia, Maier, Holger, Marschall, Susan, Micklich, Kateryna, Möller, Gabriele, Naton, Beatrix, Prehn, Cornelia, Puk, Oliver, Rácz, Ildikó, Räß, Michael, Rathkolb, Birgit, Rozman, Jan, Scheerer, Markus, Schiller, Evelyn, Schrewe, Anja, Steinkamp, Ralph, Stöger, Claudia, Sun, Minxuan, Szymczak, Wilfried, Treise, Irina, Vargas Panesso, Ingrid Liliana, Vernaleken, Alexandra M., Willershäuser, Monja, Wolff-Muscate, Annemarie, Zeh, Ramona, Adamski, Jerzy, Beckers, Johannes, Bekeredjian, Raffi, Busch, Dirk H., Eickelberg, Oliver, Favor, Jack, Graw, Jochen, Höfler, Heinz, Höschen, Christoph, Katus, Hugo, Klingenspor, Martin, Klopstock, Thomas, Neff, Frauke, Ollert, Markus, Schulz, Holger, Stöger, Tobias, Wolf, Eckhard, Wurst, Wolfgang, Yildirim, Ali Önder, Zimmer, Andreas, and Hrabě de Angelis, Martin

Published
2012
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20. Dual role of proapoptotic BAD in insulin secretion and beta cell survival

Author

Danial, Nika N., Walensky, Loren D., Zhang, Chen-Yu, Choi, Cheol Soo, Fisher, Jill K., Molina, Anthony J.A., Datta, Sandeep Robert, Pitter, Kenneth L., Bird, Gregory H., Wikstrom, Jakob D., Deeney, Jude T., Robertson, Kirsten, Morash, Joel, Kulkarni, Ameya, Neschen, Susanne, Kim, Sheene, Greenberg, Michael E., Corkey, Barbara E., Shirihai, Orian S., Shulman, Gerald I., Lowell, Bradford B., and Korsmeyer, Stanley J.

Subjects
Physiological aspects, Research, Genetic aspects, Health aspects, Pancreatic beta cells -- Health aspects -- Research -- Physiological aspects, Apoptosis -- Health aspects -- Research -- Genetic aspects -- Physiological aspects, Glucose metabolism -- Physiological aspects -- Research -- Genetic aspects -- Health aspects, Glucokinase -- Health aspects -- Genetic aspects -- Research -- Physiological aspects, Insulin -- Health aspects -- Genetic aspects -- Research
Abstract

The BCL-2 family of proteins constitutes a key control point in apoptosis by regulating the release of apoptogenic factors from mitochondria (1). Recent studies have assigned new roles to certain [...], The proapoptotic BCL-2 family member BAD resides in a glucokinase-containing complex that regulates glucose-driven mitochondrial respiration. Here, we present genetic evidence of a physiologic role for BAD in glucose-stimulated insulin secretion by beta cells. This novel function of BAD is specifically dependent upon the phosphorylation of its BH3 sequence, previously defined as an essential death domain. We highlight the pharmacologic relevance of phosphorylated BAD BH3 by using cell- permeable, hydrocarbon-stapled BAD BH3 helices that target glucokinase, restore glucose-driven mitochondrial respiration and correct the insulin secretory response in Bad-deficient islets. Our studies uncover an alternative target and function for the BAD BH3 domain and emphasize the therapeutic potential of phosphorylated BAD BH3 mimetics in selectively restoring beta cell function. Furthermore, we show that BAD regulates the physiologic adaptation of beta cell mass during high-fat feeding. Our findings provide genetic proof of the bifunctional activities of BAD in both beta cell survival and insulin secretion.

Published
2008

21. Validation of candidate phospholipid biomarkers of chronic kidney disease in hyperglycemic individuals and their organ-specific exploration in leptin receptor-deficient db/db mouse

Author

Huang, Jialing, Covic, Marcela, Huth, Cornelia, Rommel, Martina, Adam, Jonathan, Zukunft, Sven, Prehn, Cornelia, Wang, Li, Nano, Jana, Scheerer, Markus, Neschen, Susanne, Kastenmüller, Gabi, Gieger, Christian, Laxy, Michael, Schliess, Freimut, Adamski, Jerzy, Suhre, Karsten, Hrabé de Angelis, Martin, Peters, Annette, Wang-Sattler, Rui, Huang, Jialing, Covic, Marcela, Huth, Cornelia, Rommel, Martina, Adam, Jonathan, Zukunft, Sven, Prehn, Cornelia, Wang, Li, Nano, Jana, Scheerer, Markus, Neschen, Susanne, Kastenmüller, Gabi, Gieger, Christian, Laxy, Michael, Schliess, Freimut, Adamski, Jerzy, Suhre, Karsten, Hrabé de Angelis, Martin, Peters, Annette, and Wang-Sattler, Rui

Abstract

Biological exploration of early biomarkers for chronic kidney disease (CKD) in (pre)diabetic individuals is crucial for personalized management of diabetes. Here, we evaluated two candidate biomarkers of incident CKD (sphingomyelin (SM) C18:1 and phosphatidylcholine diacyl (PC aa) C38:0) concerning kidney function in hyperglycemic participants of the Cooperative Health Research in the Region of Augsburg (KORA) cohort, and in two biofluids and six organs of leptin receptor-deficient (db/db) mice and wild type controls. Higher serum concentrations of SM C18:1 and PC aa C38:0 in hyperglycemic individuals were found to be associated with lower estimated glomerular filtration rate (eGFR) and higher odds of CKD. In db/db mice, both metabolites had a significantly lower concentration in urine and adipose tissue, but higher in the lungs. Additionally, db/db mice had significantly higher SM C18:1 levels in plasma and liver, and PC aa C38:0 in adrenal glands. This cross-sectional human study confirms that SM C18:1 and PC aa C38:0 associate with kidney dysfunction in pre(diabetic) individuals, and the animal study suggests a potential implication of liver, lungs, adrenal glands, and visceral fat in their systemic regulation. Our results support further validation of the two phospholipids as early biomarkers of renal disease in patients with (pre)diabetes.

Published
2021

22. Suppression of Diacylglycerol Acyltransferase-2 (DGAT2), but Not DGAT1, with Antisense Oligonucleotides Reverses Diet-induced Hepatic Steatosis and Insulin Resistance

Author

Choi, Cheol Soo, Savage, David B., Kulkarni, Ameya, Yu, Xing Xian, Liu, Zhen-Xiang, Morino, Katsutaro, Kim, Sheene, Distefano, Alberto, Samuel, Varman T., Neschen, Susanne, Zhang, Dongyan, Wang, Amy, Zhang, Xian-Man, Kahn, Mario, Cline, Gary W., Pandey, Sanjay K., Geisler, John G., Bhanot, Sanjay, Monia, Brett P., and Shulman, Gerald I.

Published
2007
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23. Increased hypothalamic-pituitary-adrenal axis activity and hepatic insulin resistance in low-birth-weight rats

Author

Buhl, Esben S., Neschen, Susanne, Yonemitsu, Shin, Rossbacher, Joerg, Zhang, Dongyan, Morino, Katsutaro, Flyvbjerg, Allan, Perret, Pascale, Samuel, Varman, Kim, Jung, Cline, Gary W., and Petersen, Kitt Falk

Subjects
Rats -- Physiological aspects, Rattus -- Physiological aspects, Insulin resistance -- Physiological aspects, Liver -- Properties, Hypothalamic-pituitary-adrenal axis -- Properties, Biological sciences
Abstract

Individuals born with a low birth weight (LBW) have an increased prevalence of type 2 diabetes, but the mechanisms responsible for this association are unknown. Given the important role of insulin resistance in the pathogenesis of type 2 diabetes, we examined insulin sensitivity in a rat model of LBW due to intrauterine fetal stress. During the last 7 days of gestation, rat dams were treated with dexamethasone and insulin sensitivity was assessed in the LBW offspring by a hyperinsulinemic euglycemic clamp. The LBW group had liver-specific insulin resistance associated with increased levels of PEPCK expression. These changes were associated with pituitary hyperplasia of the ACTH-secreting cells, increased morning plasma ACTH concentrations, elevated corticosterone secretion during restraint stress, and an ~70% increase in 24-h urine corticosterone excretion. These data support the hypothesis that prenatal stress can result in chronic hyperactivity of the hypothalamic-pituitary-adrenal axis, resulting in increased plasma corticosterone concentrations, upregulation of hepatic gluconeogenesis, and hepatic insulin resistance. gluconeogenesis; adrenocorticotropic hormone; corticosterone; type 2 diabetes

Published
2007

24. The central melanocortin system directly controls peripheral lipid metabolism

Author

Nogueiras, Ruben, Wiedmer, Petra, Perez-Tilve, Diego, Veyrat-Durebex, Christelle, Keogh, Julia M., Sutton, Gregory M., Pfluger, Paul T., Castaneda, Tamara R., Neschen, Susanne, Hofmann, Susanna M., Howles, Philip N., Morgan, Donald A., Benoit, Stephen C., Szanto, Ildiko, Schrott, Brigitte, Schurmann, Annette, Joost, Hans-Georg, Hammond, Craig, Hui, David Y., Woods, Stephen C., Rahmouni, Kamal, Butler, Andrew A., Farooqi, I. Sadaf, O'Rahilly, Stephen, Rohner-Jeanrenaud, Francoise, and Tschop, Matthias H.

Subjects
Control, Research, Genetic aspects, Health aspects, Pituitary hormones -- Health aspects -- Research, Lipid metabolism -- Control -- Genetic aspects -- Health aspects -- Research
Abstract

Disruptions of the melanocortin signaling system have been linked to obesity. We investigated a possible role of the central nervous melanocortin system (CNS-Mcr) in the control of adiposity through effects [...]

Published
2007

25. Contrasting effects of fish oil and safflower oil on hepatic peroxisomal and tissue lipid content

Author

Neschen, Susanne, Moore, Irene, Regittnig, Werner, Yu, Chun Li, Wang, Yanlin, Pypaert, Marc, Petersen, Kitt Falk, and Shulman, Gerald I.

Subjects
Lipid metabolism -- Research, Fish oils -- Physiological aspects, Safflower oil -- Physiological aspects, Peroxisomes -- Physiological aspects, Oils and fats, Edible -- Physiological aspects, Biological sciences
Abstract

Contrasting effects of fish oil and safflower oil on hepatic peroxisomal and tissue lipid content. Am J Physiol Endocrinol Metab 282: E395-E401, 2002. First published October 23, 2001; 10.1152/ ajpendo.00414.2001.--To examine the mechanism by which fish oil protects against fat-induced insulin resistance, we studied the effects of control, fish oil, and safflower oil diets on peroxisomal content, fatty acyl-CoA, diacylglycerol, and ceramide content in rat liver and muscle. We found that, in contrast to control and safflower oil-fed rats, fish oil feeding induced a 150% increase in the abundance of peroxisomal acyl-CoA oxidase and 3-ketoacyl-CoA thiolase in liver but lacked similar effects in muscle. This was paralleled by an almost twofold increase in hepatic peroxisome content (both P < 0.002 vs. control and safflower). These changes in the fish oil-fed rats were associated with a more than twofold lower hepatic triglyceride/diacylglycerol, as well as intramuscular triglyceride/fatty acyl-CoA, content. In conclusion, these data strongly support the hypothesis that n-3 fatty acids protect against fat-induced insulin resistance by serving as peroxisome proliferator-activated receptor-[alpha] ligands and thereby induce hepatic, but not intramuscular, peroxisome proliferation. In turn, an increased hepatic [beta]-oxidative capacity results in lower hepatic triglyceride/diacylglycerol and intramyocellular triglyceride/fatty acyl-CoA content. peroxisome proliferator-activating receptor-[alpha]; [beta]-oxidation; diacylglycerol; acyl-CoA oxidase; 3-ketoacyl-CoA thiolase

Published
2002

26. Validation of Candidate Phospholipid Biomarkers of Chronic Kidney Disease in Hyperglycemic Individuals and Their Organ-Specific Exploration in Leptin Receptor-Deficient db/db Mouse

Author

Huang, Jialing, primary, Covic, Marcela, additional, Huth, Cornelia, additional, Rommel, Martina, additional, Adam, Jonathan, additional, Zukunft, Sven, additional, Prehn, Cornelia, additional, Wang, Li, additional, Nano, Jana, additional, Scheerer, Markus F., additional, Neschen, Susanne, additional, Kastenmüller, Gabi, additional, Gieger, Christian, additional, Laxy, Michael, additional, Schliess, Freimut, additional, Adamski, Jerzy, additional, Suhre, Karsten, additional, de Angelis, Martin Hrabe, additional, Peters, Annette, additional, and Wang-Sattler, Rui, additional

Published
2021
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27. Machine learning approaches revealed metabolic signatures of incident chronic kidney disease in persons with pre-and type 2 diabetes

Author

Admin, Ada, primary, Huang, Jialing, primary, Huth, Cornelia, primary, Covic, Marcela, primary, Troll, Martina, primary, Adam, Jonathan, primary, Zukunft, Sven, primary, Prehn, Cornelia, primary, Wang, Li, primary, Nano, Jana, primary, Scheerer, Markus F., primary, Neschen, Susanne, primary, Kastenmüller, Gabi, primary, Suhre, Karsten, primary, Laxy, Michael, primary, Schliess, Freimut, primary, Gieger, Christian, primary, Adamski, Jerzy, primary, Angelis, Martin Hrabe de, primary, Peters, Annette, primary, and Wang-Sattler, Rui, primary

Published
2020
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28. Machine Learning Approaches Reveal Metabolic Signatures of Incident Chronic Kidney Disease in Individuals With Prediabetes and Type 2 Diabetes

Author

Huang, Jialing, primary, Huth, Cornelia, additional, Covic, Marcela, additional, Troll, Martina, additional, Adam, Jonathan, additional, Zukunft, Sven, additional, Prehn, Cornelia, additional, Wang, Li, additional, Nano, Jana, additional, Scheerer, Markus F., additional, Neschen, Susanne, additional, Kastenmüller, Gabi, additional, Suhre, Karsten, additional, Laxy, Michael, additional, Schliess, Freimut, additional, Gieger, Christian, additional, Adamski, Jerzy, additional, Hrabe de Angelis, Martin, additional, Peters, Annette, additional, and Wang-Sattler, Rui, additional

Published
2020
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33. Muscle-specific IRS-1 Ser [right arrow] Ala transgenic mice are protected from fat-induced insulin resistance in skeletal muscle

Author

Morino, Katsutaro, Neschen, Susanne, Bilz, Stefan, Sono, Saki, Tsirigotis, Dimitrios, Reznick, Richard M., Moore, Irene, Nagai, Yoshio, Samuel, Varman, Sebastian, David, White, Morris, Philbrick, William, and Shulman, Gerald I.

Subjects
Phosphorylation -- Physiological aspects, Phosphorylation -- Research, Insulin resistance -- Development and progression, Type 2 diabetes -- Risk factors, Muscles -- Physiological aspects, Serine -- Physiological aspects, Health
Abstract

OBJECTIVE--Insulin resistance in skeletal muscle plays a critical role in the pathogenesis of type 2 diabetes, yet the cellular mechanisms responsible for insulin resistance are poorly understood. In this study, [...]

Published
2008

42. Response to Comment on Adam et al. Metformin Effect on Nontargeted Metabolite Profiles in Patients With Type 2 Diabetes and in Multiple Murine Tissues. Diabetes 2016;65:3776–3785

Author

Adam, Jonathan, primary, Brandmaier, Stefan, additional, Troll, Martina, additional, Rotter, Markus, additional, Mohney, Robert P., additional, Heier, Margit, additional, Adamski, Jerzy, additional, Li, Yixue, additional, Neschen, Susanne, additional, Kastenmüller, Gabi, additional, Suhre, Karsten, additional, Ankerst, Donna, additional, Meitinger, Thomas, additional, and Wang-Sattler, Rui, additional

Published
2017
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43. Impact of Brain Fatty Acid Signaling on Peripheral Insulin Action in Mice.

Author

Neschen, Susanne, Wu, Moya, Fuchs, Christiane, Kondofersky, Ivan, Theis, Fabian J., de Angelis, Martin Hrabě, Häring, Hans-Ulrich, and Sartorius, Tina

Subjects
*FATTY acids, *PALMITIC acid, *INSULIN, *BRAINWASHING, *ELECTROENCEPHALOGRAPHY
Abstract

Aims and Methods Glucose homeostasis and energy balance are under control by peripheral and brain processes. Especially insulin signaling in the brain seems to impact whole body glucose homeostasis and interacts with fatty acid signaling. In humans circulating saturated fatty acids are negatively associated with brain insulin action while animal studies suggest both positive and negative interactions of fatty acids and insulin brain action. This apparent discrepancy might reflect a difference between acute and chronic fatty acid signaling. To address this question we investigated the acute effect of an intracerebroventricular palmitic acid administration on peripheral glucose homeostasis. We developed and implemented a method for simultaneous monitoring of brain activity and peripheral insulin action in freely moving mice by combining radiotelemetry electrocorticography (ECoG) and euglycemic-hyperinsulinemic clamps. This method allowed gaining insight in the early kinetics of brain fatty acid signaling and its contemporaneous effect on liver function in vivo , which, to our knowledge, has not been assessed so far in mice. Results Insulin-induced brain activity in the theta and beta band was decreased by acute intracerebroventricular application of palmitic acid. Peripherally it amplified insulin action as demonstrated by a significant inhibition of endogenous glucose production and increased glucose infusion rate. Moreover, our results further revealed that the brain effect of peripheral insulin is modulated by palmitic acid load in the brain. Conclusion These findings suggest that insulin action is amplified in the periphery and attenuated in the brain by acute palmitic acid application. Thus, our results indicate that acute palmitic acid signaling in the brain may be different from chronic effects. [ABSTRACT FROM AUTHOR]

Published
2020
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44. Bezafibrate Improves Insulin Sensitivity and Metabolic Flexibility in STZ-Induced Diabetic Mice

Author

Franko, Andras, Huypens, Peter, Neschen, Susanne, Irmler, Martin, Rozman, Jan, Rathkolb, Birgit, Neff, Frauke, Prehn, Cornelia, Dubois, Guillaume, Baumann, Martina, Massinger, Rebecca, Gradinger, Daniel, Przemeck, Gerhard K. H., Repp, Birgit, Aichler, Michaela, Feuchtinger, Annette, Schommers, Philipp, Stoehr, Oliver, Sanchez-Lasheras, Carmen, Adamski, Jerzy, Peter, Andreas, Prokisch, Holger, Beckers, Johannes, Walch, Axel K., Fuchs, Helmut, Wolf, Eckhard, Schubert, Markus, Wiesner, Rudolf J., de Angelis, Martin Hrabe, Franko, Andras, Huypens, Peter, Neschen, Susanne, Irmler, Martin, Rozman, Jan, Rathkolb, Birgit, Neff, Frauke, Prehn, Cornelia, Dubois, Guillaume, Baumann, Martina, Massinger, Rebecca, Gradinger, Daniel, Przemeck, Gerhard K. H., Repp, Birgit, Aichler, Michaela, Feuchtinger, Annette, Schommers, Philipp, Stoehr, Oliver, Sanchez-Lasheras, Carmen, Adamski, Jerzy, Peter, Andreas, Prokisch, Holger, Beckers, Johannes, Walch, Axel K., Fuchs, Helmut, Wolf, Eckhard, Schubert, Markus, Wiesner, Rudolf J., and de Angelis, Martin Hrabe

Abstract

Bezafibrate (BEZ), a pan activator of peroxisome proliferator-activated receptors (PPARs), has been generally used to treat hyperlipidemia for decades. Clinical trials with type 2 diabetes patients indicated that BEZ also has beneficial effects on glucose metabolism, although the underlying mechanisms of these effects remain elusive. Even less is known about a potential role for BEZ in treating type 1 diabetes. Here we show that BEZ markedly improves hyperglycemia and glucose and insulin tolerance in mice with streptozotocin (STZ)-induced diabetes, an insulin-deficient mouse model of type 1 diabetes. BEZ treatment of STZ mice significantly suppressed the hepatic expression of genes that are annotated in inflammatory processes, whereas the expression of PPAR and insulin target gene transcripts was increased. Furthermore, BEZ-treated mice also exhibited improved metabolic flexibility as well as an enhanced mitochondria! mass and function in the liver. Finally, we show that the number of pancreatic islets and the area of insulin-positive cells tended to be higher in BEZ-treated mice. Our data suggest that BEZ may improve impaired glucose metabolism by augmenting hepatic mitochondria) performance, suppressing hepatic inflammatory pathways, and improving insulin sensitivity and metabolic flexibility. Thus, BEZ treatment might also be useful for patients with impaired glucose tolerance or diabetes.

Published
2016

45. Metformin Effect on Nontargeted Metabolite Profiles in Patients With Type 2 Diabetes and in Multiple Murine Tissues

Author

Adam, Jonathan, primary, Brandmaier, Stefan, additional, Leonhardt, Jörn, additional, Scheerer, Markus F., additional, Mohney, Robert P., additional, Xu, Tao, additional, Bi, Jie, additional, Rotter, Markus, additional, Troll, Martina, additional, Chi, Shen, additional, Heier, Margit, additional, Herder, Christian, additional, Rathmann, Wolfgang, additional, Giani, Guido, additional, Adamski, Jerzy, additional, Illig, Thomas, additional, Strauch, Konstantin, additional, Li, Yixue, additional, Gieger, Christian, additional, Peters, Annette, additional, Suhre, Karsten, additional, Ankerst, Donna, additional, Meitinger, Thomas, additional, Hrabĕ de Angelis, Martin, additional, Roden, Michael, additional, Neschen, Susanne, additional, Kastenmüller, Gabi, additional, and Wang-Sattler, Rui, additional

Published
2016
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46. Bezafibrate Improves Insulin Sensitivity and Metabolic Flexibility in STZ-Induced Diabetic Mice

Author

Franko, Andras, primary, Huypens, Peter, additional, Neschen, Susanne, additional, Irmler, Martin, additional, Rozman, Jan, additional, Rathkolb, Birgit, additional, Neff, Frauke, additional, Prehn, Cornelia, additional, Dubois, Guillaume, additional, Baumann, Martina, additional, Massinger, Rebecca, additional, Gradinger, Daniel, additional, Przemeck, Gerhard K.H., additional, Repp, Birgit, additional, Aichler, Michaela, additional, Feuchtinger, Annette, additional, Schommers, Philipp, additional, Stöhr, Oliver, additional, Sanchez-Lasheras, Carmen, additional, Adamski, Jerzy, additional, Peter, Andreas, additional, Prokisch, Holger, additional, Beckers, Johannes, additional, Walch, Axel K., additional, Fuchs, Helmut, additional, Wolf, Eckhard, additional, Schubert, Markus, additional, Wiesner, Rudolf J., additional, and Hrabě de Angelis, Martin, additional

Published
2016
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47. Thiazolidinediones PPAR[Gamma]-Independently Inhibit Palmitate Oxidation of Rat Skeletal Muscle In Vitro

Author

FURNSINN, CLEMENS, BRUNMAIR, BARBARA, GRAS, FLORIAN, NESCHEN, SUSANNE, RODEN, MICHAEL, and WALDHAUSL, WERNER

Subjects
Physiological aspects, Research, Diabetes research -- Physiological aspects, Thiazolidinediones -- Physiological aspects -- Research, Diabetes -- Research
Abstract

Thiazolidinediones (TZD) are antidiabetic agents believed to induce insulin sensitization via the activation of nuclear PPAR[Gamma] receptors resulting in the modulation of gene transcription rates. In previous studies on isolated [...]

Published
2000

48. eIF6 coordinates insulin sensitivity and lipid metabolism by coupling translation to transcription

Author

Brina, Daniela, primary, Miluzio, Annarita, additional, Ricciardi, Sara, additional, Clarke, Kim, additional, Davidsen, Peter K., additional, Viero, Gabriella, additional, Tebaldi, Toma, additional, Offenhäuser, Nina, additional, Rozman, Jan, additional, Rathkolb, Birgit, additional, Neschen, Susanne, additional, Klingenspor, Martin, additional, Wolf, Eckhard, additional, Gailus-Durner, Valerie, additional, Fuchs, Helmut, additional, Hrabe de Angelis, Martin, additional, Quattrone, Alessandro, additional, Falciani, Francesco, additional, and Biffo, Stefano, additional

Published
2015
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50. Troglitazone Inhibits [CO.sub.2] Production from Glucose and Palmitate in Rat Skeletal Muscle in vitro

Author

FURNSINN, CLEMENS, BRUNMAIR, BARBARA, NESCHEN, SUSANNE, RODEN, MICHAEL, and WALDHAUSL, WERNER

Subjects
Research, Diabetes research, Diabetes -- Research
Abstract

Troglitazone is believed to induce insulin sensitization by modulating gene transcription via the activation of nuclear PPAR [Gamma] receptors. To investigate the direct effects of troglitazone on skeletal muscle, freshly [...]

Published
1999

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