Brain glucagon-like peptide 1 signaling controls the onset of high-fat diet-induced insulin resistance and reduces energy expenditure.
2008
Knauf, Claude | Cani, Patrice, D. | Ait-Belgnaoui, Afifa | Benani, Alexandre | Dray, Cédric | Cabou, Cendrine | Colom, André | Uldry, Marc | Rastrelli, Sophie | Sabatier, Eric | Godet, Natacha | Waget, Aurélie | Pénicaud, Luc | Valet, Philippe | Burcelin, Rémy | Institut de médecine moléculaire de Rangueil (I2MR) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Unit of Pharmacokinetics, Metabolism, Nutrition, and Toxicology (PMNT-73/69) ; Université Catholique de Louvain = Catholic University of Louvain (UCL) | Neuro-Gastroentérologie et Nutrition (NGN) ; Institut National de la Recherche Agronomique (INRA)-Ecole supérieure d'agriculture de Purpan (ESAP) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT) | Métabolisme Plasticité et Mitochondrie [lié à l'ex IFR 31] (LMPM) ; IFR 31 Louis Bugnard (IFR 31) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) | Dana-Farber Cancer Institute [Boston]
International audience
Show more [+] Less [-]English. 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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