K S Weber1, K Straßburger2, M Fritsch3, A Bierwagen1, C Koliaki4, E Phielix5, G Pacini6, J-H Hwang1, D F Markgraf1, V Burkart1, K Müssig7, J Szendroedi7, M Roden8. 1. Institute for Clinical Diabetology, German Diabetes Centre at Heinrich Heine University, Leibniz Centre for Diabetes Research, Düsseldorf, Germany; German Centre for Diabetes Research (DZD), München-Neuherberg, Germany. 2. German Centre for Diabetes Research (DZD), München-Neuherberg, Germany; Institute for Biometrics and Epidemiology, German Diabetes Centre at Heinrich Heine University, Leibniz Centre for Diabetes Research, Düsseldorf, Germany. 3. Institute for Clinical Diabetology, German Diabetes Centre at Heinrich Heine University, Leibniz Centre for Diabetes Research, Düsseldorf, Germany; German Centre for Diabetes Research (DZD), München-Neuherberg, Germany; Department of Pediatric and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. 4. Institute for Clinical Diabetology, German Diabetes Centre at Heinrich Heine University, Leibniz Centre for Diabetes Research, Düsseldorf, Germany; German Centre for Diabetes Research (DZD), München-Neuherberg, Germany; Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Athens University Medical School, Athens, Greece. 5. Institute for Clinical Diabetology, German Diabetes Centre at Heinrich Heine University, Leibniz Centre for Diabetes Research, Düsseldorf, Germany; German Centre for Diabetes Research (DZD), München-Neuherberg, Germany; Department of Human Biology and Movement Sciences, NUTRIM school for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, Netherlands. 6. Metabolic Unit, Institute of Neuroscience, National Research Council, Padova, Italy. 7. Institute for Clinical Diabetology, German Diabetes Centre at Heinrich Heine University, Leibniz Centre for Diabetes Research, Düsseldorf, Germany; German Centre for Diabetes Research (DZD), München-Neuherberg, Germany; Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 8. Institute for Clinical Diabetology, German Diabetes Centre at Heinrich Heine University, Leibniz Centre for Diabetes Research, Düsseldorf, Germany; German Centre for Diabetes Research (DZD), München-Neuherberg, Germany; Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. Electronic address: michael.roden@ddz.uni-duesseldorf.de.
Abstract
AIM: Type 2 diabetes (T2D) alters glucagon, glucagon-like peptide (GLP)-1, glucose-dependent insulinotropic polypeptide (GIP) and hepatic energy metabolism, yet the possible relationships remain unclear. METHODS: In this observational study, lean insulin-sensitive control subjects (BMI: 23.2±1.5kg/m2), age-matched insulin-resistant obese subjects (BMI: 34.3±1.7kg/m2) and similarly obese elderly T2D patients (BMI: 32.0±2.4kg/m2) underwent mixed-meal tolerance tests (MMTTs), and assessment of hepatic γATP, inorganic phosphate (Pi) and lipids using 31P/1H magnetic resonance spectroscopy. Meal-induced secretion of glucagon and incretins was calculated from incremental areas under the concentration-time curves (iAUCs). Peripheral and adipose tissue insulin sensitivity were assessed from time courses of circulating glucose, insulin and free fatty acids. RESULTS: MMTT-derived peripheral insulin sensitivity was lowest in T2D patients (P<0.001), while glucagon concentrations were comparable across all three groups. At 260min, GLP-1 was lower in T2D patients than in controls, whereas GIP was lowest in obese individuals. Fasting glucagon concentrations correlated positively with fasting (r=0.60) and postprandial hepatocellular lipid levels (160min: r=0.51, 240min: r=0.59), and negatively with adipose tissue insulin sensitivity (r=-0.73). Higher meal-induced glucagon release (iAUC0-260min) correlated with lower fasting (r=-0.62) and postprandial Pi levels (160min: r=-0.43, 240min: r=-0.42; all P<0.05). Higher meal-induced release of GIP (iAUC0-260min) correlated positively with fasting (r=0.54) and postprandial serum triglyceride concentrations (iAUC0-260min, r=0.54; all P<0.01). CONCLUSION: Correlations between fasting glucagon and hepatic lipids and between meal-induced glucagon and hepatic Pi suggest a role for glucagon in hepatic energy metabolism.
AIM: Type 2 diabetes (T2D) alters glucagon, glucagon-like peptide (GLP)-1, glucose-dependent insulinotropic polypeptide (GIP) and hepatic energy metabolism, yet the possible relationships remain unclear. METHODS: In this observational study, lean insulin-sensitive control subjects (BMI: 23.2±1.5kg/m2), age-matched insulin-resistant obese subjects (BMI: 34.3±1.7kg/m2) and similarly obese elderly T2D patients (BMI: 32.0±2.4kg/m2) underwent mixed-meal tolerance tests (MMTTs), and assessment of hepatic γATP, inorganic phosphate (Pi) and lipids using 31P/1H magnetic resonance spectroscopy. Meal-induced secretion of glucagon and incretins was calculated from incremental areas under the concentration-time curves (iAUCs). Peripheral and adipose tissue insulin sensitivity were assessed from time courses of circulating glucose, insulin and free fatty acids. RESULTS: MMTT-derived peripheral insulin sensitivity was lowest in T2D patients (P<0.001), while glucagon concentrations were comparable across all three groups. At 260min, GLP-1 was lower in T2D patients than in controls, whereas GIP was lowest in obese individuals. Fasting glucagon concentrations correlated positively with fasting (r=0.60) and postprandial hepatocellular lipid levels (160min: r=0.51, 240min: r=0.59), and negatively with adipose tissue insulin sensitivity (r=-0.73). Higher meal-induced glucagon release (iAUC0-260min) correlated with lower fasting (r=-0.62) and postprandial Pi levels (160min: r=-0.43, 240min: r=-0.42; all P<0.05). Higher meal-induced release of GIP (iAUC0-260min) correlated positively with fasting (r=0.54) and postprandial serum triglyceride concentrations (iAUC0-260min, r=0.54; all P<0.01). CONCLUSION: Correlations between fasting glucagon and hepatic lipids and between meal-induced glucagon and hepatic Pi suggest a role for glucagon in hepatic energy metabolism.
Authors: Theresa Kössler; Pavel Bobrov; Klaus Strassburger; Oliver Kuss; Oana-Patricia Zaharia; Yanislava Karusheva; Clara Möser; Kálmán Bódis; Volker Burkart; Michael Roden; Julia Szendroedi Journal: Nutr Metab (Lond) Date: 2021-05-04 Impact factor: 4.169
Authors: Yanislava Karusheva; Theresa Koessler; Klaus Strassburger; Daniel Markgraf; Lucia Mastrototaro; Tomas Jelenik; Marie-Christine Simon; Dominik Pesta; Oana-Patricia Zaharia; Kálmán Bódis; Felix Bärenz; Dieter Schmoll; Martin Wolkersdorfer; Andrea Tura; Giovanni Pacini; Volker Burkart; Karsten Müssig; Julia Szendroedi; Michael Roden Journal: Am J Clin Nutr Date: 2019-11-01 Impact factor: 7.045