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.
Type de document :
Article dans une revue
Endocrinology, Endocrine Society, 2008, 149 (10), pp.4768-77. 〈10.1210/en.2008-0180〉
Liste complète des métadonnées

http://www.hal.inserm.fr/inserm-00409099
Contributeur : Marie Francoise Simon <>
Soumis le : mercredi 5 août 2009 - 16:51:46
Dernière modification le : jeudi 13 septembre 2018 - 10:30:07

Lien texte intégral

Identifiants

Collections

Citation

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〉

Partager

Métriques

Consultations de la notice

339