Jump to ContentJump to Main Navigation

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

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

12 Issues per year


IMPACT FACTOR increased in 2014: 3.268
Rank 106 out of 289 in category Biochemistry & Molecular Biology in the 2014 Thomson Reuters Journal Citation Report/Science Edition

VolumeIssuePage

Issues

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

Victor A. Gault1 / Kerry Hunter2 / Nigel Irwin3 / Brett Greer4 / Brian D. Green5 / Patrick Harriott6 / Finbarr P.M. O'Harte7 / Peter R. Flatt8

1.

2.

3.

4.

5.

6.

7.

8.

Corresponding author

Citation Information: Biological Chemistry. Volume 388, Issue 2, Pages 173–179, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2007.019, January 2007

Publication History

Received:
June 21, 2006
Accepted:
September 29, 2006
Published Online:
2007-01-29

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

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[2]
P L McClean, N Irwin, K Hunter, V A Gault, and P R Flatt
British Journal of Pharmacology, 2009, Volume 155, Number 5, Page 690
[3]
Ying Sun, Lin Wang, Minghu Jiang, Juxiang Huang, Zhenqiu Liu, and Stefan Wolfl
Cell Biochemistry and Biophysics, 2010, Volume 56, Number 2-3, Page 59

Comments (0)

Please log in or register to comment.