| Detection of extracellular glucose by GLUT2 contributes to hypothalamic control of food intake. | |
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MedLine Citation:
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PMID: 20179244 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The sugar transporter GLUT2, present in several tissues of the gut-brain axis, has been reported to be involved in the control of food intake. GLUT2 is a sugar transporter sustaining energy production in the cell, but it can also function as a receptor for extracellular glucose. A glucose-signaling pathway is indeed triggered, independently of glucose metabolism, through its large cytoplasmic loop domain. However, the contribution of the receptor function over the transporter function of GLUT2 in the control of food intake remains to be determined. Thus, we generated transgenic mice that express a GLUT2-loop domain, blocking the detection of glucose but leaving GLUT2-dependent glucose transport unaffected. Inhibiting GLUT2-mediated glucose detection augmented daily food intake by a mechanism that increased the meal size but not the number of meals. Peripheral hormones (ghrelin, insulin, leptin) were unaffected, leading to a focus on central aspects of feeding behavior. We found defects in c-Fos activation by glucose in the arcuate nucleus and changes in the amounts of TRH and orexin neuropeptide mRNA, which are relevant to poorly controlled meal size. Our data provide evidence that glucose detection by GLUT2 contributes to the control of food intake by the hypothalamus. The sugar transporter receptor, i.e., "transceptor" GLUT2, may constitute a drug target to treat eating disorders and associated metabolic diseases, particularly by modulating its receptor function without affecting vital sugar provision by its transporter function. |
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Authors:
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Emilie Stolarczyk; Christophe Guissard; Aur?lien Michau; Patrick C Even; Alexandra Grosfeld; Patricia Serradas; Anne Lorsignol; Luc P?nicaud; Edith Brot-Laroche; Armelle Leturque; Maude Le Gall |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-23 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: 298 ISSN: 1522-1555 ISO Abbreviation: Am. J. Physiol. Endocrinol. Metab. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-14 Completed Date: 2010-05-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: E1078-87 Citation Subset: IM |
Affiliation:
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Unit? Mixte de Recherche (UMR) S872, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de m?decine, Paris, F-75006 France. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Biological Transport / physiology Body Weight / physiology Cell Count Eating / physiology* Energy Metabolism Feeding Behavior / physiology Ghrelin / blood Glucose / metabolism* Glucose Transporter Type 2 / genetics, metabolism* Homeostasis / physiology Hypothalamus / metabolism* Immunohistochemistry Insulin / blood Intracellular Signaling Peptides and Proteins / genetics, metabolism Leptin / blood Mice Mice, Transgenic Neuropeptides / genetics, metabolism Proto-Oncogene Proteins c-fos / metabolism RNA, Messenger / genetics, metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / physiology Statistics, Nonparametric Thyrotropin-Releasing Hormone / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Ghrelin; 0/Glucose Transporter Type 2; 0/Intracellular Signaling Peptides and Proteins; 0/Leptin; 0/Neuropeptides; 0/Proto-Oncogene Proteins c-fos; 0/RNA, Messenger; 0/orexins; 11061-68-0/Insulin; 24305-27-9/Thyrotropin-Releasing Hormone; 50-99-7/Glucose |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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