1. Academic Validation
  2. Arcuate glucagon-like peptide 1 receptors regulate glucose homeostasis but not food intake

Arcuate glucagon-like peptide 1 receptors regulate glucose homeostasis but not food intake

  • Diabetes. 2008 Aug;57(8):2046-54. doi: 10.2337/db07-1824.
Darleen A Sandoval 1 Didier Bagnol Stephen C Woods David A D'Alessio Randy J Seeley
Affiliations

Affiliation

  • 1 Departments of Psychiatry and Medicine, University of Cincinnati, Cincinnati, Ohio, USA. darleen.sandoval@uc.edu
Abstract

Objective: Glucagon-like peptide-1 (GLP-1) promotes glucose homeostasis through regulation of islet hormone secretion, as well as hepatic and gastric function. Because GLP-1 is also synthesized in the brain, where it regulates food intake, we hypothesized that the central GLP-1 system regulates glucose tolerance as well.

Research design and methods: We used glucose tolerance tests and hyperinsulinemic-euglycemic clamps to assess the role of the central GLP-1 system on glucose tolerance, Insulin secretion, and hepatic and peripheral Insulin sensitivity. Finally, in situ hybridization was used to examine colocalization of GLP-1 receptors with neuropeptide tyrosine and pro-opiomelanocortin neurons.

Results: We found that central, but not peripheral, administration of low doses of a GLP-1 Receptor antagonist caused relative hyperglycemia during a glucose tolerance test, suggesting that activation of central GLP-1 receptors regulates key processes involved in the maintenance of glucose homeostasis. Central administration of GLP-1 augmented glucose-stimulated Insulin secretion, and direct administration of GLP-1 into the arcuate, but not the paraventricular, nucleus of the hypothalamus reduced hepatic glucose production. Consistent with a role for GLP-1 receptors in the arcuate, GLP-1 Receptor mRNA was found to be expressed in 68.1% of arcuate neurons that expressed pro-opiomelanocortin mRNA but was not significantly coexpressed with neuropeptide tyrosine.

Conclusions: These data suggest that the arcuate GLP-1 receptors are a key component of the GLP-1 system for improving glucose homeostasis by regulating both Insulin secretion and glucose production.

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