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Chronic treatment with exendin(9-39)amide indicates a minor role for endogenous glucagon-like peptide-1 in metabolic abnormalities of obesity-related diabetes in ob/ob mice

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Green, BD, Irwin, Nigel, Gault, Victor, Bailey, CJ, O'Harte, Finbarr and Flatt, Peter (2005) Chronic treatment with exendin(9-39)amide indicates a minor role for endogenous glucagon-like peptide-1 in metabolic abnormalities of obesity-related diabetes in ob/ob mice. JOURNAL OF ENDOCRINOLOGY, 185 (2). pp. 307-317. [Journal article]

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DOI: 10.1677/joe.1.05876

Abstract

Glucagon-like peptide-1 (GLP-1) is a potent insulinotropic hormone proposed to play a role in both the pathophysiology and treatment of type 2 diabetes, This study has employed the GLP-1 receptor antagonist, exendin-4(9-39)amide (Ex(9-39)) to evaluate the role of endogenous GLP-1 in genetic obesity-related diabetes and related metabolic abnormalities using ob/ob and normal mice. Acute in vivo antagonistic potency of Ex(9-39) was confirmed in ob/ob mice by blockade of the insulin-releasing and anti-hyperglycaemic actions of intraperitoneal GLP-1. In longer term studies, ob/ob mice were given once daily injections of Ex(9-39) or vehicle for 11 days. Feeding activity, body weight, and both basal and glucose-stimulated insulin secretion were not significantly affected by chronic Ex(9-39) treatment. However, significantly elevated basal glucose concentrations and impaired glucose tolerance were evident at 11 days. These disturbances in glucose homeostasis were independent of changes of insulin sensitivity and reversed by discontinuation of the Ex(9-39) for 9 days. Similar treatment of normal mice did not affect any of the parameters measured. These findings illustrate the physiological extrapancreatic glucose-lowering actions of GLP-1 in ob/ob mice and suggest that the endogenous hormone plays a minor role in the metabolic abnormalities associated with obesity-related diabetes.

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:3001
Deposited By:Professor Peter Flatt
Deposited On:18 Dec 2009 10:04
Last Modified:19 Nov 2012 16:21

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