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Thomas, Douglas D.

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Volume 389, Issue 2 (Feb 2008)


Effects of gastric inhibitory polypeptide (GIP) and related analogues on glucagon release at normo- and hyperglycaemia in Wistar rats and isolated islets

Roslyn S. Cassidy
  • 1School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
/ Nigel Irwin
  • 2School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
    The first two authors contributed equally to this work.
/ Peter R. Flatt
  • 3School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
Published Online: 2008-01-28 | DOI: https://doi.org/10.1515/BC.2008.019


Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone secreted by endocrine K-cells in response to nutrient absorption. This study has utilised numerous well-characterised dipeptidyl peptidase IV-resistant GIP analogues to evaluate the glucagonotropic actions of GIP in Wistar rats and isolated rat islets. Intraperitoneal administration of GIP analogues (25 nmol/kg body weight) in combination with glucose had no effect on circulating glucagon concentrations compared to controls in Wistar rats. However, plasma glucose concentrations were significantly (p<0.05 to p<0.001) lowered by the GIP-receptor agonists, N-AcGIP, GIP(Lys37)PAL and N-AcGIP(Lys37)PAL. The GIP antagonist, (Pro3)GIP, caused a significant (p<0.05) reduction in glucagon levels following concurrent administration with saline in Wistar rats. In isolated rat islets native GIP induced a significant (p<0.01) enhancement of glucagon release at basal glucose concentrations, which was completely annulled by (Pro3)GIP. Furthermore, glucagon release in the presence of GLP-1, GIP(Lys37)PAL, N-AcGIP(Lys37)PAL and (Pro3)GIP was significantly (p<0.05 to p<0.001) decreased compared to native GIP in isolated rat islets. These data indicate a modest effect of GIP on glucagon secretion from isolated rat islets, which was not observed in vivo. However, the GIP agonists N-AcGIP, GIP(Lys37)PAL and N-AcGIP(Lys37)PAL had no effect on glucagon release demonstrating an improved therapeutic potential for the treatment of type 2 diabetes.

Keywords: GIP analogue; glucagon; glucose-dependent insulinotropic polypeptide (GIP); islet

About the article

Corresponding author

Received: 2007-10-09

Accepted: 2007-11-02

Published Online: 2008-01-28

Published in Print: 2008-02-01

Citation Information: Biological Chemistry, ISSN (Online) 14374315, ISSN (Print) 14316730, DOI: https://doi.org/10.1515/BC.2008.019. Export Citation

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