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Comparison of the metabolic effects of GIP receptor antagonism and PYY(3-36) receptor activation in high fat fed mice

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Irwin, Nigel, Hunter, Kerry and Flatt, Peter (2007) Comparison of the metabolic effects of GIP receptor antagonism and PYY(3-36) receptor activation in high fat fed mice. PEPTIDES, 28 (11). pp. 2192-2198. [Journal article]

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DOI: 10.1016/j.peptides.2007.08.008

Abstract

Glucose-dependent insulinotropic polypeptide (GIP) and peptide YY (PYY) are secreted from the intestinal K- and L-cells, respectively, following a meal. Both peptides are believed to play a key role in glucose homeostasis and energy expenditure. This study investigated the effects of daily administration of the stable and specific GIP-R antagonist, (Pro)GIP (25 nmol/ kg) and the endogenous truncated form of PYY, PYY(3-36) (50 nmol/kg), in mice fed with a high fat diet. Daily i.p. injection of (Pro(3))GIP, PYY(3-36) or combined peptide administration over 24 days significantly (P < 0.05-0.01) decreased body weight compared with saline-treated controls without change in food intake. Plasma glucose levels and glucose tolerance were significantly (P < 0.05) lowered by (Pro(3))GIP treatment alone, and in combination with PYY(3-36). These changes were accompanied by a slight improvement of insulin sensitivity in all of the treatment groups. (Pro(3))GIP treatment significantly reduced plasma corticosterone (P < 0.05), while combined administration with PYY(3-36) significantly lowered serum glucagon (P < 0.05). No appreciable changes were observed in either circulating or glucose-stimulated insulin secretion in all treatment groups. (Pro(3))GIP-treated mice had significantly (P < 0.01) lowered fasting glucose levels and an improved (P < 0.05) glycemic response to feeding. These comparative data indicate that chemical ablation of GIP receptor action using (Pro(3))GIP provides an especially effective means of countering obesity and related abnormalities induced by consumption of high fat energy rich diet. (C) 2007 Elsevier Inc. All rights reserved.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:2926
Deposited By:Professor Peter Flatt
Deposited On:17 Dec 2009 11:16
Last Modified:19 Nov 2012 16:02

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