Central Nervous System GLP-1 Receptors Regulate Islet Hormone Secretion and Glucose Homeostasis in Male Rats.

Published

Journal Article

The glucagon-like peptide 1 (GLP-1) system plays an important role in blood glucose regulation, in great part through coordinate control of insulin and glucagon secretion. These effects are generally attributed to GLP-1 produced in peripheral sites, principally the intestine. GLP-1 is also produced in hindbrain neurons that signal through GLP-1 receptors (GLP-1rs) expressed in brain regions involved in metabolic regulation. GLP-1 in the central nervous system (CNS) induces satiety, visceral illness, and stress responses. However, recent evidence suggests CNS GLP-1 is also involved in glucose regulation. To test the hypothesis that central GLP-1 regulates islet hormone secretion, conscious rats were given intracerebroventricular (ICV) GLP-1, GLP-1r antagonist exendin-[9-39] (Ex-9), or saline during fasting or hyperglycemia from intravenous glucose. Administration of CNS GLP-1 increased fasting glucose, glucagon, corticosterone, and epinephrine and blunted insulin secretion in response to hyperglycemia. Paradoxically, GLP-1r blockade with ICV Ex-9 also reduced glucose-stimulated insulin secretion, and administration of ICV Ex-9 to freely feeding rats caused mild glucose intolerance. Thus, direct administration of CNS GLP-1 affected islet hormone secretion counter to what is seen with peripherally administered GLP-1, an effect likely due to stimulation of sympathetic nervous system activity. In contrast, blockade of brain GLP-1r supports a role for CNS GLP-1 on glucose-stimulated insulin secretion and glucose control after a meal. These findings suggest a model in which activation of CNS GLP-1r by endogenous peptide promotes glucose tolerance, an effect that can be overridden by stress responses stimulated by exogenous GLP-1.

Full Text

Duke Authors

Cited Authors

  • Jessen, L; Smith, EP; Ulrich-Lai, Y; Herman, JP; Seeley, RJ; Sandoval, D; D'Alessio, D

Published Date

  • July 1, 2017

Published In

Volume / Issue

  • 158 / 7

Start / End Page

  • 2124 - 2133

PubMed ID

  • 28430981

Pubmed Central ID

  • 28430981

Electronic International Standard Serial Number (EISSN)

  • 1945-7170

Digital Object Identifier (DOI)

  • 10.1210/en.2016-1826

Language

  • eng

Conference Location

  • United States