1: Diabetes. 2008 Oct;57(10):2603-12. Epub 2008 Jun 2.

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

Knauf C, Cani PD, Kim DH, Iglesias MA, Chabo C, Waget A, Colom A, Rastrelli S,
Delzenne NM, Drucker DJ, Seeley RJ, Burcelin R.

Institut de Medecine Moleculaire de Rangueil, Institut National de la Santé et de
la Recherche Médicale U858, IFR31, Centre Hospitalier Universitaire Rangueil,
Toulouse, France.

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.

PMCID: PMC2551668 [Available on 10/01/09]
PMID: 18519802 [PubMed - in process]

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