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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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IMPACT FACTOR 2015: 2.710
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Online
ISSN
1437-4315
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Volume 388, Issue 2 (Feb 2007)

Issues

Characterisation and glucoregulatory actions of a novel acylated form of the (Pro3)GIP receptor antagonist in type 2 diabetes

Victor A. Gault
  • School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
/ Kerry Hunter
  • School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
/ Nigel Irwin
  • School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
/ Brett Greer
  • School of Biological Sciences, Queen's University of Belfast, Belfast BT9 7BL, Northern Ireland, UK
/ Brian D. Green
  • School of Biological Sciences, Queen's University of Belfast, Belfast BT9 7BL, Northern Ireland, UK
/ Patrick Harriott
  • School of Biological Sciences, Queen's University of Belfast, Belfast BT9 7BL, Northern Ireland, UK
/ Finbarr P.M. O'Harte
  • School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
/ Peter R. Flatt
  • School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
Published Online: 2007-01-29 | DOI: https://doi.org/10.1515/BC.2007.019

Abstract

In this study, we tested the biological activity of a novel acylated form of (Pro3)glucose-dependent insulinotropic polypetide [(Pro3)GIP] prepared by conjugating palmitic acid to Lys16 to enhance its efficacy in vivo by promoting binding to albumin and extending its biological actions. Like the parent molecule (Pro3)GIP, (Pro3)GIPLys16PAL was completely stable to the actions of DPP-IV and significantly (p<0.01 to p<0.001) inhibited GIP-stimulated cAMP production and cellular insulin secretion. Furthermore, acute administration of (Pro3)GIPLys16PAL also significantly (p<0.05 to p<0.001) countered the glucose-lowering and insulin-releasing actions of GIP in ob/ob mice. Daily injection of (Pro3)GIPLys16PAL (25 nmol/kg bw) in 14–18-week-old ob/ob mice over 14 days had no effect on body weight, food intake or non-fasting plasma glucose and insulin concentrations. (Pro3)GIPLys16PAL treatment also failed to significantly alter the glycaemic response to an i.p. glucose load or test meal, but insulin concentrations were significantly reduced (1.5-fold; p<0.05) after the glucose load. Insulin sensitivity was enhanced (1.3-fold; p<0.05) and pancreatic insulin was significantly reduced (p<0.05) in the (Pro3)GIPLys16PAL-treated mice. These data demonstrate that acylation of Lys16 with palmitic acid in (Pro3)GIP does not improve its biological effectiveness as a GIP receptor antagonist.

Keywords: antihyperglycaemic activity; DPP IV; fatty acid-linked peptides; GIP receptor antagonists; insulin secretion; obese diabetic (ob/ob) mice

References

About the article

Corresponding author


Received: June 21, 2006

Accepted: September 29, 2006

Published Online: 2007-01-29

Published in Print: 2007-02-01


Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2007.019. Export Citation

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