ECE2016 Oral Communications Diabetes prediction & complications (5 abstracts)
Glucose-dependent insulinotropic peptide (GIP) stimulates Glucagon-like peptide (GLP)-1 from human and mouse pancreatic islets partly via alpha-cell-derived IL-6
Katharina Timper 1, , Elise Dalmas 1 , Erez Dror 1 , Sabine Rütti 4, , Constanze Thienel 1 , Nadine S. Sauter 1 , Karim Bouzakri 3 , Benoit Bédat 5 , Francois Pattou 6 , Julie Kerr-Conte 6 , Marianne Böni-Schnetzler 1 & Marc Y. Donath 1
1Department of Biomedicine, Clinic of Endocrinology, Diabetes and Metabolism, University Hospital and University of Basel, Basel, Switzerland; 2Max-Planck-Institute for Metabolism Research, Cologne, Germany; 3CUM, Departement de Medecine Genetique & Development, Geneva, Switzerland; 4Département de Physiologie, Lausanne, Switzerland; 5Department of Surgery, Cell Isolation and Transplantation Center, Geneva University Hospitals and University of Geneva School of Medicine, Geneva, Switzerland; 6University Lille Nord de France, Lille, France.
Introduction: Glucose-dependent insulinotropic peptide (GIP) induces the cytokine interleukin (IL)-6 in adipocytes. IL-6 enhances insulin secretion from β-cells via L- and α-cell-derived GLP-1.Therefore we hypothesized that GIP regulates Glucagon-like peptide (GLP)-1 as well as glucose control via IL-6.
Methods/Design: Basic research study on isolated human and mouse pancreatic islets and FACS-sorted human α-and β-cells that were treated with GIP in vitro. For in vivo studies, GIP effects on GLP-1 and insulin secretion as well as glucose homeostasis were evaluated in mouse models with pharmacologic and genetic ablation of IL-6.
Results: GIP induced IL-6 in mouse and human pancreatic α-cells, leading to GLP-1 and insulin secretion in pancreatic islets. This effect was impaired in the absence of IL-6 and modulated by IL-1β which stimulated IL-6 but directly impaired GLP-1 production. Furthermore, inhibition of the sodium glucose transporter (SGLT)2 with dapagliflozin - enhanced GIP-induced GLP-1 release. In vivo, GIP increased plasma GLP-1 and insulin, and improved glucose tolerance, which was potentiated by lipopolysaccharide and strongly decreased in IL-6-deficient mice or in the presence of a blocking anti-IL-6 antibody. In diabetic mice, IL-1β and IL-6 were massively upregulated in isolated islets and GIP lost its effects on glycaemia control and GLP-1 induction.
Conclusion: These data indicate that GIP induces GLP-1 and insulin via α-cell-derived IL-6, and that this effect is modulated by IL-1β and SGLT2 inhibtion. During diabetes, the prevailing inflammation may attenuate GIP effects. These findings further support the concept that the immune system plays an integral role in the regulation of metabolism in physiology and pathology.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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