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

87 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

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Central Nervous System
Glucose
Pro-Opiomelanocortin
Neuropeptide Y
Brain
Glycogen
Knockout Mice
Glucagon-Like Peptide-1 Receptor
Neurons
Muscles
Arcuate Nucleus of Hypothalamus
High Fat Diet
Green Fluorescent Proteins
Cell Nucleus
Hypothalamus
Brain Stem
Veins
Homeostasis
Research Design
Fats

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Knauf, C., Cani, P. D., Kim, D-H., Iglesias, M. A., Chabo, C., Waget, A., ... 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

Role of central nervous system glucagon-like peptide-1 receptors in enteric glucose sensing. / Knauf, Claude; Cani, Patrice D.; Kim, Dong-Hun; Iglesias, Miguel A.; Chabo, Chantal; Waget, Aurélie; Colom, André; Rastrelli, Sophie; Delzenne, Nathalie M.; Drucker, Daniel J.; Seeley, Randy J.; Burcelin, Remy.

In: Diabetes, Vol. 57, No. 10, 01.10.2008, p. 2603-2612.

Research output: Contribution to journalArticle

Knauf, C, Cani, PD, Kim, D-H, Iglesias, MA, Chabo, C, Waget, A, Colom, A, Rastrelli, S, Delzenne, NM, Drucker, DJ, Seeley, RJ & Burcelin, R 2008, 'Role of central nervous system glucagon-like peptide-1 receptors in enteric glucose sensing', Diabetes, vol. 57, no. 10, pp. 2603-2612. https://doi.org/10.2337/db07-1788
Knauf, Claude ; Cani, Patrice D. ; Kim, Dong-Hun ; Iglesias, Miguel A. ; Chabo, Chantal ; Waget, Aurélie ; Colom, André ; Rastrelli, Sophie ; Delzenne, Nathalie M. ; Drucker, Daniel J. ; Seeley, Randy J. ; Burcelin, Remy. / Role of central nervous system glucagon-like peptide-1 receptors in enteric glucose sensing. In: Diabetes. 2008 ; Vol. 57, No. 10. pp. 2603-2612.
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AU - Chabo, Chantal

AU - Waget, Aurélie

AU - Colom, André

AU - Rastrelli, Sophie

AU - Delzenne, Nathalie M.

AU - Drucker, Daniel J.

AU - Seeley, Randy J.

AU - Burcelin, Remy

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N2 - 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.

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