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Metabolic effects of sub-chronic ablation of the incretin receptors by daily administration of (Pro(3))GIP and exendin(9-39)amide in obese diabetic (ob/ob) mice

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

Parker, Jeremy C, Irwin, Nigel, Lavery, Kerry S, Green, Brian D, O'Harte, Finbarr, Gault, Victor and Flatt, Peter (2007) Metabolic effects of sub-chronic ablation of the incretin receptors by daily administration of (Pro(3))GIP and exendin(9-39)amide in obese diabetic (ob/ob) mice. BIOLOGICAL CHEMISTRY, 388 (2). pp. 221-226. [Journal article]

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DOI: 10.1515/BC.2007.024

Abstract

Effects of chemical ablation of the GIP and GLP-1 receptors on metabolic aspects of obesity-diabetes were investigated using the stable receptor antagonists (Pro(3))GIP and exendin(9-39)amide. Ob/ob mice received a daily i.p. injection of saline vehicle, (Pro(3))GIP, exendin(9-39)amide or a combination of both peptides over a 14-day period. Non-fasting plasma glucose levels were significantly (p < 0.05) lower in (Pro(3))GIP-treated mice compared to control mice after just 9 days of treatment. (Pro(3))GIP-treated mice also displayed significantly lower plasma glucose concentrations in response to feeding and intraperitoneal administration of either glucose or insulin (p < 0.05 to p < 0.001). The (Pro(3))GIP-treated group also exhibited significantly (p < 0.05) reduced pancreatic insulin content. Acute administration of exendin(9-39) amide immediately prior to re-feeding completely annulled the beneficial effects of sub-chronic (Pro(3))GIP treatment, but non-fasting concentrations of active GLP-1 were unchanged. Combined sub-chronic administration of (Pro(3)GIP) with exendin(9-39)amide revealed no beneficial effects. Similarly, daily administration of exendin(9-39)amide alone had no significant effects on any of the metabolic parameters measured. These studies highlight an important role for GIP in obesity-related forms of diabetes, suggesting the possible involvement of GLP-1 in the beneficial actions of GIP receptor antagonism.

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:2957
Deposited By:Professor Peter Flatt
Deposited On:17 Dec 2009 15:00
Last Modified:19 Nov 2012 16:07

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