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Brain glucagon-like peptide-1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage

Citation

Knauf, C and Cani, PD and Perrin, C and Iglesias, MA and Maury, JF and Bernard, E and Benhamed, F and Gremeaux, T and Drucker, DJ and Kahn, CR and Girard, J and Tanti, JF and Delzenne, NM and Postic, C and Burcelin, R, Brain glucagon-like peptide-1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage, Journal of Clinical Investigation, 115, (12) pp. 3554-63. ISSN 0021-9738 (2005) [Refereed Article]


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Copyright Statement

Copyright 2005 American Society for Clinical Investigation

DOI: doi:10.1172/JCI25764

Abstract

Intestinal glucagon-like peptide-1 (GLP-1) is a hormone released into the hepatoportal circulation that stimulates pancreatic insulin secretion. GLP-1 also acts as a neuropeptide to control food intake and cardiovascular functions, but its neural role in glucose homeostasis is unknown. We show that brain GLP-1 controlled whole-body glucose fate during hyperglycemic conditions. In mice undergoing a hyperglycemic hyperinsulinemic clamp, icv administration of the specific GLP-1 receptor antagonist exendin 9-39 (Ex9) increased muscle glucose utilization and glycogen content. This effect did not require muscle insulin action, as it also occurred in muscle insulin receptor KO mice. Conversely, icv infusion of the GLP-1 receptor agonist exendin 4 (Ex4) reduced insulin-stimulated muscle glucose utilization. In hyperglycemia achieved by i.v. infusion of glucose, icv Ex4, but not Ex9, caused a 4-fold increase in insulin secretion and enhanced liver glycogen storage. However, when glucose was infused intragastrically, icv Ex9 infusion lowered insulin secretion and hepatic glycogen levels, whereas no effects of icv Ex4 were observed. In diabetic mice fed a high-fat diet, a 1-month chronic i.p. Ex9 treatment improved glucose tolerance and fasting glycemia. Our data show that during hyperglycemia, brain GLP-1 inhibited muscle glucose utilization and increased insulin secretion to favor hepatic glycogen stores, preparing efficiently for the next fasting state.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Medical Biochemistry and Metabolomics
Research Field:Metabolic Medicine
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Diabetes
Author:Iglesias, MA (Dr Miguel Iglesias)
ID Code:80261
Year Published:2005
Web of Science® Times Cited:190
Deposited By:Health Sciences A
Deposited On:2012-10-25
Last Modified:2012-11-27
Downloads:0

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