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Cell Metab. 2007 Jun;5(6):438-49.

Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production.

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  • 1Department of Mouse Genetics and Metabolism, Institute for Genetics, Center for Molecular Medicine, University of Cologne, D-50674 Cologne, Germany.

Abstract

Insulin action in the central nervous system regulates energy homeostasis and glucose metabolism. To define the insulin-responsive neurons that mediate these effects, we generated mice with selective inactivation of the insulin receptor (IR) in either pro-opiomelanocortin (POMC)- or agouti-related peptide (AgRP)-expressing neurons of the arcuate nucleus of the hypothalamus. While neither POMC- nor AgRP-restricted IR knockout mice exhibited altered energy homeostasis, insulin failed to normally suppress hepatic glucose production during euglycemic-hyperinsulinemic clamps in AgRP-IR knockout (IR(DeltaAgRP)) mice. These mice also exhibited reduced insulin-stimulated hepatic interleukin-6 expression and increased hepatic expression of glucose-6-phosphatase. These results directly demonstrate that insulin action in POMC and AgRP cells is not required for steady-state regulation of food intake and body weight. However, insulin action specifically in AgRP-expressing neurons does play a critical role in controlling hepatic glucose production and may provide a target for the treatment of insulin resistance in type 2 diabetes.

PMID:
17550779
DOI:
10.1016/j.cmet.2007.05.004
[PubMed - indexed for MEDLINE]
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