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Maria Gomez

Maria Gomez

Professor

Maria Gomez

Pleiotropic Effects of GIP on Islet Function Involve Osteopontin

Author

  • Valeriya Lyssenko
  • Lena Eliasson
  • Olga Kotova
  • Kasper Pilgaard
  • Nils Wierup
  • S Albert Salehi
  • Anna Wendt
  • Anna Jonsson
  • Yang Z. De Marinis
  • Lisa Berglund
  • Jalal Taneera
  • Alexander Balhuizen
  • Ola Hansson
  • Peter Osmark
  • Pontus Dunér
  • Charlotte Brons
  • Alena Stancakova
  • Johanna Kuusisto
  • Marco Bugliani
  • Richa Saxena
  • Emma Ahlqvist
  • Timothy J. Kieffer
  • Tiinamaija Tuomi
  • Bo Isomaa
  • Olle Melander
  • Emily Sonestedt
  • Marju Orho-Melander
  • Peter Nilsson
  • Sara Bonetti
  • Riccardo Bonadonna
  • Roberto Miccoli
  • Stefano DelPrato
  • Piero Marchetti
  • Sten Madsbad
  • Pernille Poulsen
  • Allan Vaag
  • Markku Laakso
  • Maria Gomez
  • Leif Groop

Summary, in English

OBJECTIVE-The incretin hormone GIP (glucose-dependent insulinotropic polypeptide) promotes pancreatic beta-cell function by potentiating insulin secretion and beta-cell proliferation. Recently, a combined analysis of several genome-wide association studies (Meta-analysis of Glucose and Insulin-Related Traits Consortium [MAGIC]) showed association to postprandial insulin at the GIP receptor (GIPR) locus. Here we explored mechanisms that could explain the protective effects of GIP on islet function. RESEARCH DESIGN AND METHODS-Associations of GIPR rs10423928 with metabolic and anthropometric phenotypes in both nondiabetic (N = 53,730) and type 2 diabetic individuals (N = 2,731) were explored by combining data from 11 studies.Insulin secretion was measured both in vivo in nondiabetic subjects and in vitro in islets from cadaver donors. Insulin secretion was also measured in response to exogenous GIP. The in vitro measurements included protein and gene expression as well as measurements of beta-cell viability and proliferation. RESULTS-The A allele of GIPR rs10423928 was associated with impaired glucose- and GIP-stimulated insulin secretion and a decrease in BMI, lean body mass, and waist circumference. The decrease in BMI almost completely neutralized the effect of impaired insulin secretion on risk of type 2 diabetes. Expression of GIPR mRNA was decreased in human islets from carriers of the A allele or patients with type 2 diabetes. GIP stimulated osteopontin (OPN) mRNA and protein expression. OPN expression was lower in carriers of the A allele. Both GIP and OPN prevented cytokine-induced reduction in cell viability (apoptosis). In addition, OPN stimulated cell proliferation in insulin-secreting cells. CONCLUSIONS-These findings support beta-cell proliferative and antiapoptotic roles for GIP in addition to its action as an incretin hormone. Identification of a link between GIP and OPN may shed new light on the role of GIP in preservation of functional beta-cell mass in humans. Diabetes 60:2424-2433, 2011

Department/s

  • Genomics, Diabetes and Endocrinology
  • Department of Clinical Sciences, Malmö
  • Diabetes - Islet Cell Exocytosis
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Diabetes - Molecular Metabolism
  • Neuroendocrine Cell Biology
  • Islet cell physiology
  • Vascular Physiology
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Cardiovascular Research - Hypertension
  • Nutrition Epidemiology
  • Internal Medicine - Epidemiology
  • EpiHealth: Epidemiology for Health

Publishing year

2011

Language

English

Pages

2424-2433

Publication/Series

Diabetes

Volume

60

Issue

9

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Diabetes - Islet Cell Exocytosis
  • Diabetes - Molecular Metabolism
  • Neuroendocrine Cell Biology
  • Islet cell physiology
  • Vascular Physiology
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Cardiovascular Research - Hypertension
  • Nutrition Epidemiology
  • Internal Medicine - Epidemiology

ISBN/ISSN/Other

  • ISSN: 1939-327X