Role of central nervous system glucagon-like peptide-1 receptors in enteric glucose sensing

Claude Knauf, Patrice D. Cani, Dong-Hun Kim, Miguel A. Iglesias, Chantal Chabo, Aurélie Waget, André Colom, Sophie Rastrelli, Nathalie M. Delzenne, Daniel J. Drucker, Randy J. Seeley, Remy Burcelin

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

OBJECTIVE-Ingested glucose is detected by specialized sensors in the enteric/hepatoportal vein, which send neural signals to the brain, which in turn regulates key peripheral tissues. Hence, impairment in the control of enteric-neural glucose sensing could contribute to disordered glucose homeostasis. The aim of this study was to determine the cells in the brain targeted by the activation of the enteric glucose-sensing system. RESEARCH DESIGN AND METHODS-We selectively activated the axis in mice using a low-rate intragastric glucose infusion in wild-type and glucagon-like peptide-1 (GLP-1) receptor knockout mice, neuropeptide Y- and proopiomelanocortin- green fluorescent protein-expressing mice, and high-fat diet diabetic mice. We quantified the whole-body glucose utilization rate and the pattern of c-Fos positive in the brain. RESULTS-Enteric glucose increased muscle glycogen synthesis by 30% and regulates c-Fos expression in the brainstem and the hypothalamus. Moreover, the synthesis of muscle glycogen was diminished after central infusion of the GLP-1 receptor (GLP-1Rc) antagonist Exendin 9-39 and abolished in GLP-1Rc knockout mice. Gut-glucose-sensitive c-Fos-positive cells of the arcuate nucleus colocalized with neuropeptide Y-positive neurons but not with proopiomelanocortin-positive neurons. Furthermore, high-fat feeding prevented the enteric activation of c-Fos expression. CONCLUSIONS-We conclude that the gut-glucose sensor modulates peripheral glucose metabolism through a nutrient- sensitive mechanism, which requires brain GLP-1Rc and is impaired during diabetes.

Original languageEnglish
Pages (from-to)2603-2612
Number of pages10
JournalDiabetes
Volume57
Issue number10
DOIs
Publication statusPublished - 2008 Oct 1
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Knauf, C., Cani, P. D., Kim, D-H., Iglesias, M. A., Chabo, C., Waget, A., Colom, A., Rastrelli, S., Delzenne, N. M., Drucker, D. J., Seeley, R. J., & Burcelin, R. (2008). Role of central nervous system glucagon-like peptide-1 receptors in enteric glucose sensing. Diabetes, 57(10), 2603-2612. https://doi.org/10.2337/db07-1788