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Comparison of independent and combined chronic metabolic effects of GIP and CB1 receptor blockade in high-fat fed mice

Irwin, Nigel, Hunter, Kerry and Flatt, Peter (2008) Comparison of independent and combined chronic metabolic effects of GIP and CB1 receptor blockade in high-fat fed mice. PEPTIDES, 29 (6). pp. 1036-1041. [Journal article]

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DOI: 10.1016/j.peptides.2008.01.006


GIP receptor antagonism with (Pro(3))GIP protects against obesity, insulin resistance, glucose intolerance and associated disturbances in mice fed high-fat diet. Furthermore, cannabinoid CBI receptor antagonism with AM251 reduces appetite and body weight gain in mice. The present study has examined and compared the effects of chronic daily administrations of (Pro(3))GIP (25 nmol/kg body weight), AM251 (6 mg/kg body weight) and a combination of both drugs in high-fat fed mice. Daily i.p. injection of (Pro(3))GIP, AM251 or combined drug administration over 22 days significantly (P < 0.05 to P < 0.01) decreased body weight compared with saline-treated controls. This was associated with a significant (P < 0.05 to P < 0.01) reduction of food intake in mice treated with AM251. Plasma glucose levels and glucose tolerance were significantly (P < 0.05) lowered by 22 days (Pro)GIP, AM251 or combined drug treatment. These changes were accompanied by a significant (P < 0.05) improvement of insulin sensitivity in all treatment groups. In contrast, AM251 lacked effects on glucose tolerance, metabolic response to feeding and insulin sensitivity in high-fat mice when administered acutely. These data indicate that chemical blockade of GIP- or CB1-receptor signaling using (Pro(3))GIP or AM251, respectively provides an effective means of countering obesity and related abnormalities induced by consumption of high-fat energy-rich diet. AM251 lacks acute effects on glucose homeostasis and there was no evidence of a synergistic effect of combined treatment with (Pro(3))GIP. (C) 2008 Elsevier Inc. All rights reserved.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:2914
Deposited By: Professor Peter Flatt
Deposited On:17 Dec 2009 10:07
Last Modified:19 Nov 2012 15:55

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