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Brain glucagon-like peptide 1 signaling controls the onset of high-fat diet-induced insulin resistance and reduces energy expenditure.

Abstract : Glucagon-like peptide-1 (GLP-1) is a peptide released by the intestine and the brain. We previously demonstrated that brain GLP-1 increases glucose-dependent hyperinsulinemia and insulin resistance. These two features are major characteristics of the onset of type 2 diabetes. Therefore, we investigated whether blocking brain GLP-1 signaling would prevent high-fat diet (HFD)-induced diabetes in the mouse. Our data show that a 1-month chronic blockage of brain GLP-1 signaling by exendin-9 (Ex9), totally prevented hyperinsulinemia and insulin resistance in HFD mice. Furthermore, food intake was dramatically increased, but body weight gain was unchanged, showing that brain GLP-1 controlled energy expenditure. Thermogenesis, glucose utilization, oxygen consumption, carbon dioxide production, muscle glycolytic respiratory index, UCP2 expression in muscle, and basal ambulatory activity were all increased by the exendin-9 treatment. Thus, we have demonstrated that in response to a HFD, brain GLP-1 signaling induces hyperinsulinemia and insulin resistance and decreases energy expenditure by reducing metabolic thermogenesis and ambulatory activity.
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https://www.hal.inserm.fr/inserm-00409099
Contributor : Marie Francoise Simon <>
Submitted on : Wednesday, August 5, 2009 - 4:51:46 PM
Last modification on : Monday, November 23, 2020 - 9:16:07 AM

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Claude Knauf, Patrice Cani, Afifa Ait-Belgnaoui, Alexandre Benani, Cédric Dray, et al.. Brain glucagon-like peptide 1 signaling controls the onset of high-fat diet-induced insulin resistance and reduces energy expenditure.. Endocrinology, Endocrine Society, 2008, 149 (10), pp.4768-77. ⟨10.1210/en.2008-0180⟩. ⟨inserm-00409099⟩

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