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experiments that the incretin effect, i.e., the augmented insulin secretion seen after oral vs i.v. glucose, is increased in insulin-resistant mice (3) and that the β-cell responsiveness to intravenous glucagon-like peptide-1 (GLP1) is augmented (3, 4
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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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Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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Introduction Glucagon and glucagon-like peptide-1 (GLP-1) are processed from the same precursor, proglucagon ( Fig. 1 ), and have opposite effects on glucose homeostasis ( 1 , 2 , 3 ). In the intestine, proglucagon is cleaved by prohormone
Danish Diabetes Academy, Odense University Hospital, Odense, Denmark
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Department of Public Health, Research Unit of Epidemiology, Aarhus University, Aarhus, Denmark
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Department of Public Health, Research Unit of Epidemiology, Aarhus University, Aarhus, Denmark
Steno Diabetes Center Aarhus, Aarhus, Denmark
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Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
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National Institute of Public Health, University of Southern Denmark, Odense, Denmark
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Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
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for premature mortality ( 4 ). Glucagon-like peptide-1 (GLP-1) is a peptide hormone secreted from intestinal L-cells upon meal intake ( 5 ). GLP-1 stimulates insulin secretion in a glucose-dependent manner – as part of ‘the incretin effect’ – being
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). Incretin hormones are released after meal ingestion and account for up to 70% of postprandial insulin secretion ( 3 ). Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide are the most important incretin hormones. GLP-1 secretion is impaired
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the treatment of glomerular diseases and key targets for the prevention and treatment of glomerular diseases ( 10 , 11 ). Glucagon-like peptide-1 (GLP-1) is an endogenous entero-insulinotropic hormone whose main target of action is GLP-1 receptor
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investigated. Animal studies have consistently shown that RS improves glucose and insulin metabolism through increased postprandial GLP1 secretion due to stimulation of the colonic enteroendocrine cells (8, 9) . This can result in improved insulin secretion
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Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden, Dresden, Germany
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Comprehensive Heart Failure Center, Würzburg, Germany
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, the success of RYGB lies in changes of gut hormone levels relevant for food intake behavior. Elevated levels of glucagon-like peptide 1 (GLP-1), peptide tyrosine tyrosine (PYY), glucose-dependent insulinotropic polypeptide (GIP) and oxyntomodulin were
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Faculty of Medicine, University of Latvia, Riga, Latvia
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-body insulin resistance ( 8 , 9 ). This article aims to not only observe novel strategies in the treatment of diabesity but also to describe the unique qualities of previously unseen hormone cross links between insulin, glucagon, and GLP-1. Overview of
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Glucose-like peptide-1 (GLP-1) is a vital hormone in the intestines that regulates glucose metabolism. Although pancreatic derived factor (PANDER) overexpression is known to suppress GLP-1, the underlying mechanisms are unclear. Our study aims to uncover how PANDER influences GLP-1 synthesis and secretion. We established a PANDER overexpression model in STC-1 intestinal cells, confirming its inhibitory effect on GLP-1 secretion. This effect was reversed in PANDER-knockout cells. Additionally, a negative correlation between PANDER and GLP-1 was observed in patients with gestational diabetes history. Subsequently, through whole transcriptome gene sequencing in PANDER-overexpressed STC-1 cells, we discovered that the activation of IL-6 and its related STAT3 signaling pathway was significantly inhibited, and this finding was validated by WB and QPCR. Finally, rescue experiments confirmed that the IL-6-related STAT3/Akt/GSK3β/β-catenin signaling pathway mediates the negative regulatory effect of PANDER on GLP-1. Taken together, our data identify IL-6 as a bridge connecting PANDER and GLP-1 in the STC-1 cells, demonstrating the potential therapeutic targets for diabetes treatment by targeting PANDER-IL-6-GLP-1 axis.
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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i) whether i.v. glucose per se could affect thyroid function parameters and ii) whether any changes could be elicited by infusion of the gastrointestinal hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP1