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


Knauf, C and Cani, PD and Kim, DH and Iglesias, MA and Chabo, C and Waget, A and Colom, C and Rastrell, S and Delzenne, NM and Drucker, DJ and Seeley, RJ and Burcelin, R, Role of central nervous system glucagon-like Peptide-1 receptors in enteric glucose sensing, Diabetes, 57, (10) pp. 2603-12. ISSN 0012-1797 (2008) [Refereed Article]

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Copyright Statement

Copyright 2012 American Diabetes Association

DOI: doi:10.2337/db07-1788


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 signaling and is impaired during diabetes.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Medical biochemistry and metabolomics
Research Field:Metabolic medicine
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Iglesias, MA (Dr Miguel Iglesias)
ID Code:80186
Year Published:2008
Web of Science® Times Cited:92
Deposited By:Health Sciences A
Deposited On:2012-10-24
Last Modified:2012-11-27

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