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

Roslyn S. Cassidy1 / Nigel Irwin2 / Peter R. Flatt3

1School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK

2School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
The first two authors contributed equally to this work.

3School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK

Corresponding author

Citation Information: Biological Chemistry. Volume 389, Issue 2, Pages 189–193, ISSN (Online) 14374315, ISSN (Print) 14316730, DOI: 10.1515/BC.2008.019, January 2008

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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

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