NDLI: [Val12] HRAS downregulates GLUT2 in beta cells of transgenic mice without affecting glucose homeostasis.

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[Val12] HRAS downregulates GLUT2 in beta cells of transgenic mice without affecting glucose homeostasis.

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[Val12] HRAS downregulates GLUT2 in beta cells of transgenic mice without affecting glucose homeostasis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Surana, M. Fleischer, N. Weir, G. Tal, M. Wu, Y. J. Leiser, M. Efrat, S. Lodish, H.
Description	Author Affiliation: Tal M ( Whitehead Institute for Biomedical Research, Cambridge, MA 02142.);
Abstract	Glucose-induced insulin release from pancreatic beta cells depends on the beta-cell metabolism of glucose, which generates intracellular signals for secretion. The beta-cell glucose transporter isotype GLUT2 and the glucose phosphorylating enzyme glucokinase have both been implicated in coupling insulin secretion to extracellular glucose levels. Here we present evidence that a pronounced decrease in beta-cell GLUT2 has no immediate effect on glucose homeostasis. Analysis of transgenic mice overexpressing human [Val12]HRAS oncoprotein under control of the insulin promoter reveals a great reduction in plasma-membrane GLUT2 levels. These mice are nonetheless able to maintain normal fed and fasting plasma glucose and insulin levels for a period of several months. Insulin secretion studied in isolated islets and the perfused pancreas is characterized by a normal incremental response to increasing glucose concentrations. Glucose metabolism, as measured by glucose phosphorylation and oxidation in isolated islets, shows a normal dose dependence on extracellular glucose concentrations. These findings suggest that normal GLUT2 expression in beta cells is not essential for glucose sensing. The transgenic mice provide an experimental system for studying the role of glucose phosphorylation in regulation of insulin release in the absence of GLUT2.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	13
Volume Number	89
Language	English
Publisher	National Academy of Sciences
Publisher Date	1992-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Genes, Ras Glucokinase Metabolism Glucose Islets Of Langerhans Physiology Monosaccharide Transport Proteins Animals Blotting, Western Fluorescent Antibody Technique Hexokinase Homeostasis Insulin Mice Mice, Transgenic Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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