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

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

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91 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

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