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). Additionally, the time of the day of an OGTT seems to influence the glucose response with higher post-load blood glucose levels in the afternoon and evening compared to the morning ( 1 , 3 ). The incretin hormones glucagon-like peptide 1 (GLP-1) and glucose
Department of Endocrinology, Diabetes and Metabolic Diseases, Normandie Univ, UNIROUEN, Rouen University Hospital, Rouen, France
Centre d’Investigation Clinique (CIC-CRB)-INSERM 1404, Rouen University Hospital, Rouen, France
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Department of Endocrinology, Diabetes and Metabolic Diseases, Normandie Univ, UNIROUEN, Rouen University Hospital, Rouen, France
Centre d’Investigation Clinique (CIC-CRB)-INSERM 1404, Rouen University Hospital, Rouen, France
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Centre d’Investigation Clinique (CIC-CRB)-INSERM 1404, Rouen University Hospital, Rouen, France
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that this neuropeptide regulates glycemia by acting as an incretin ( 24 ). In humans, an association between the 26RFa/GPR103 system and the regulation of glucose homeostasis is far more limited. This observation prompted us to investigate in detail
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Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China
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. Incretin-based drugs, including glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 (DPP-4) inhibitors, may offer an opportunity to avoid these side effects. Theoretically, GLP-1 RAs are structurally and functionally similar to
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Department of Medicine, Gentofte and Herlev Hospital, University of Copenhagen, Denmark
Steno Diabetes Center Copenhagen, Gentofte, Denmark
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Novartis Healthcare A/S, Copenhagen, Denmark
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Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Department of Medicine, Gentofte and Herlev Hospital, University of Copenhagen, Denmark
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chronic hyperglucagonemia and a severely reduced incretin effect ( 3 , 4 , 5 ). The incretin effect refers to the greater insulin response during oral glucose ingestion compared to isoglycemic intravenous (IV) glucose infusion (IIGI) ( 5 ). The incretin
Turku PET Centre, University of Turku, Turku, Finland
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several potential vasoactive substances increase ( 8 ). In rodents, experimental hyperglycemia increases and hypoglycemia decreases pancreatic islet perfusion ( 9 ). Moreover, incretins have been shown to regulate BF in the splanchnic and systemic
Department of Medicine, Department of Biomedical Sciences, Department of Endocrinology, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, Denmark
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Department of Medicine, Department of Biomedical Sciences, Department of Endocrinology, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, Denmark
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Department of Medicine, Department of Biomedical Sciences, Department of Endocrinology, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, Denmark
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Department of Medicine, Department of Biomedical Sciences, Department of Endocrinology, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, Denmark
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during both oral and i.v. glucose and thereby contribute to the observed TSH suppression patterns (11) . Also, as GIP and GLP1 increase somatostatin secretion, at least in animals (34) , suppression of TSH during incretin infusion might have been
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incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) account for the gut-derived amplification of insulin secretion ( 4 ). In addition to the effect on pancreatic islets, we ( 5 ) and others ( 6 ) have
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Obesity is a major cause of type 2 diabetes. Transition from obesity to type 2 diabetes manifests in the dysregulation of hormones controlling glucose homeostasis and inflammation. As metabolism is a dynamic process that changes across 24 h, we assessed diurnal rhythmicity in a panel of 10 diabetes-related hormones. Plasma hormones were analysed every 2 h over 24 h in a controlled laboratory study with hourly isocaloric drinks during wake. To separate effects of body mass from type 2 diabetes, we recruited three groups of middle-aged men: an overweight (OW) group with type 2 diabetes and two control groups (lean and OW). Average daily concentrations of glucose, triacylglycerol and all the hormones except visfatin were significantly higher in the OW group compared to the lean group (P < 0.001). In type 2 diabetes, glucose, insulin, C-peptide, glucose-dependent insulinotropic peptide and glucagon-like peptide-1 increased further (P < 0.05), whereas triacylglycerol, ghrelin and plasminogen activator inhibitor-1 concentrations were significantly lower compared to the OW group (P < 0.001). Insulin, C-peptide, glucose-dependent insulinotropic peptide and leptin exhibited significant diurnal rhythms in all study groups (P < 0.05). Other hormones were only rhythmic in 1 or 2 groups. In every group, hormones associated with glucose regulation (insulin, C-peptide, glucose-dependent insulinotropic peptide, ghrelin and plasminogen activator inhibitor-1), triacylglycerol and glucose peaked in the afternoon, whereas glucagon and hormones associated with appetite and inflammation peaked at night. Thus being OW with or without type 2 diabetes significantly affected hormone concentrations but did not affect the timing of the hormonal rhythms.
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( 4 ). Alternatively, incretin mimetic drugs are a relatively new group of drugs used in the treatment of diabetes that are currently recommended by American Diabetes Association in dual therapy with metformin for the treatment of T2D ( 5 , 6 ). The