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Role of central nervous system glucagon-like Peptide-1 receptors in enteric glucose sensing
journal contributionposted on 2023-05-17, 13:44 authored by Knauf, C, Cani, PD, Kim, DH, Miguel IglesiasMiguel Iglesias, Chabo, C, Waget, A, Colom, C, Rastrell, S, Delzenne, NM, Drucker, DJ, Seeley, RJ, Burcelin, R
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.
Department/SchoolSchool of Health Sciences
PublisherAmer Diabetes Assoc
Place of publication1701 N Beauregard St, Alexandria, USA, Va, 22311-1717
Rights statementCopyright 2012 American Diabetes Association