1: Endocrinology. 2008 Oct;149(10):4768-77. Epub 2008 Jun 12.

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

Knauf C, Cani PD, Ait-Belgnaoui A, Benani A, Dray C, Cabou C, Colom A, Uldry M,
Rastrelli S, Sabatier E, Godet N, Waget A, Pénicaud L, Valet P, Burcelin R.

Institut de Medecine Moleculaire de Rangueil, Toulouse III University, Centre
Hospitalier Universitaire Rangueil, BP84225, 31432 Toulouse Cedex 4, France.

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.


PMID: 18556349 [PubMed - in process]

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