JOE
HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Journal of Endocrinology (2005) 185, 307-317    DOI: 10.1677/joe.1.05876
© 2005 Society for Endocrinology
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Green, B D
Right arrow Articles by Flatt, P R
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Green, B D
Right arrow Articles by Flatt, P R

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

B D Green, N Irwin, V A Gault, C J Bailey1, F P M O’Harte and P R Flatt

School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, United Kingdom
1 School of Pharmaceutical and Biological Sciences, Aston University, Birmingham, UK

(Requests for offprints should be addressed to B D Green; Email: b.green{at}ulster.ac.uk)

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.




This article has been cited by other articles:


Home page
 EndocrinologyHome page
Z.-L. Chu, C. Carroll, J. Alfonso, V. Gutierrez, H. He, A. Lucman, M. Pedraza, H. Mondala, H. Gao, D. Bagnol, et al.
A Role for Intestinal Endocrine Cell-Expressed G Protein-Coupled Receptor 119 in Glycemic Control by Enhancing Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Peptide Release
Endocrinology, May 1, 2008; 149(5): 2038 - 2047.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
B. D. Green, K. S. Lavery, N. Irwin, F. P. M. O'Harte, P. Harriott, B. Greer, C. J. Bailey, and P. R. Flatt
Novel Glucagon-Like Peptide-1 (GLP-1) Analog (Val8)GLP-1 Results in Significant Improvements of Glucose Tolerance and Pancreatic beta-Cell Function after 3-Week Daily Administration in Obese Diabetic (ob/ob) Mice
J. Pharmacol. Exp. Ther., August 1, 2006; 318(2): 914 - 921.
[Abstract] [Full Text] [PDF]


HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2005 by the Society for Endocrinology.