High-Fat Diet-Induced Diabetes Involves Brain Pathway

Blocking pathway prevents hyperinsulinema and insulin resistance

THURSDAY, June 19 (HealthDay News) -- Mice fed a high-fat diet do not become diabetic if a signaling pathway in the brain regulating insulin levels and insulin resistance is blocked, according to research published online June 12 in Endocrinology.

Claude Knauf, from Toulouse III University in Toulouse, France, and colleagues treated mice fed a high-fat diet, which normally develop diabetes before the onset of obesity, with Exendin-9 intracerebrally to block brain glucagon-like peptide-1 (GLP-1) signaling. They had previously shown that brain GLP-1 increases glucose-dependent hyperinsulinemia and insulin resistance.

The researchers found that blocking GLP-1 for one month prevented hyperinsulinemia and insulin resistance, dramatically reduced food intake without affecting body weight gain, and increased thermogenesis, glucose use, oxygen use, carbon dioxide production, muscle glycolytic respiratory index, muscle uncoupling protein 2 expression and basal ambulatory activity.

"Thus we have demonstrated that in response to a high-fat diet, brain GLP-1 signaling induces hyperinsulinemia, insulin resistance, and decreases energy expenditure by reducing metabolic thermogenesis and ambulatory activity," Knauf and colleagues conclude.

Two of the study authors are supported by grants from Merck Sharpe and Dohme Chibret, ALFEDIAM/Novartis, and EFSD-Amylin.

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