Role of central nervous system glucagon-like Peptide-1 receptors in enteric glucose sensing
| Autor: | Daniel J. Drucker, Rémy Burcelin, Miguel A. Iglesias, Dong Hoon Kim, Aurélie Waget, Patrice D. Cani, Sophie Rastrelli, André Colom, Claude Knauf, Nathalie M. Delzenne, Randy J. Seeley, Chantal Chabo |
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| Přispěvatelé: | Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Unit of Pharmacokinetics, Metabolism, Nutrition, and Toxicology (PMNT-73/69), Université Catholique de Louvain = Catholic University of Louvain (UCL), Department of Psychiatry, University of Cincinnati (UC)-Genome Research Institute, Banting and Best Diabetes Centre, Samuel Lunenfeld Research Institute-Mt. Sinai Hospital, University of Toronto, UCL - MD/FARM - Ecole de pharmacie, Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Blood Glucose
Central Nervous System Endocrinology Diabetes and Metabolism MESH: Glycogen MESH: Mice Knockout chemistry.chemical_compound Mice 0302 clinical medicine Glucagon-Like Peptide 1 Receptors Glucagon Glucose homeostasis Insulin MESH: Animals Receptor Mice Knockout 0303 health sciences MESH: Muscle Skeletal Glycogen MESH: Proto-Oncogene Proteins c-fos digestive oral and skin physiology Brain Glucagon-like peptide-1 Immunohistochemistry MESH: Glucose Liver Hypothalamus Proto-Oncogene Proteins c-fos medicine.medical_specialty Neuropeptide 030209 endocrinology & metabolism MESH: Insulin Carbohydrate metabolism Biology Glucagon-Like Peptide-1 Receptor 03 medical and health sciences MESH: Receptors Glucagon MESH: Brain MESH: Mice Inbred C57BL Internal medicine Internal Medicine medicine Animals MESH: Central Nervous System Glycogen synthase Muscle Skeletal MESH: Mice 030304 developmental biology MESH: Glucagon-Like Peptide 1 MESH: Immunohistochemistry Mice Inbred C57BL Metabolism Endocrinology Glucose chemistry biology.protein MESH: Blood Glucose MESH: Liver |
| Zdroj: | Diabetes Diabetes, American Diabetes Association, 2008, 57 (10), pp.2603-12. ⟨10.2337/db07-1788⟩ Diabetes, Vol. 57, no. 10, p. 2603-2612 (2008) Diabetes, 2008, 57 (10), pp.2603-12. ⟨10.2337/db07-1788⟩ |
| ISSN: | 0012-1797 1939-327X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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