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

Michael Tal, Y. Jian Wu, Margarita Leiser, Manju Surana, Harvey Lodish, Norman Fleischer, Gordon Weir, Shimon Efrath

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Glucose-induced insulin release from pancreatic β cells depends on the β-cell metabolism of glucose, which generates intracellular signals for secretion. The β-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 β-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 β 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.

Original languageEnglish (US)
Pages (from-to)5744-5748
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number13
StatePublished - Jul 1 1992

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Transgenic Mice
Homeostasis
Down-Regulation
Glucose
Insulin
Phosphorylation
Glucokinase
Facilitative Glucose Transport Proteins
Oncogene Proteins
Pancreas
Fasting
Cell Membrane

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

[Val12]HRAS downregulates GLUT2 in β cells of transgenic mice without affecting glucose homeostasis. / Tal, Michael; Wu, Y. Jian; Leiser, Margarita; Surana, Manju; Lodish, Harvey; Fleischer, Norman; Weir, Gordon; Efrath, Shimon.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 13, 01.07.1992, p. 5744-5748.

Research output: Contribution to journalArticle

Tal, M, Wu, YJ, Leiser, M, Surana, M, Lodish, H, Fleischer, N, Weir, G & Efrath, S 1992, '[Val12]HRAS downregulates GLUT2 in β cells of transgenic mice without affecting glucose homeostasis', Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 13, pp. 5744-5748.
Tal, Michael ; Wu, Y. Jian ; Leiser, Margarita ; Surana, Manju ; Lodish, Harvey ; Fleischer, Norman ; Weir, Gordon ; Efrath, Shimon. / [Val12]HRAS downregulates GLUT2 in β cells of transgenic mice without affecting glucose homeostasis. In: Proceedings of the National Academy of Sciences of the United States of America. 1992 ; Vol. 89, No. 13. pp. 5744-5748.
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AU - Wu, Y. Jian

AU - Leiser, Margarita

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AU - Lodish, Harvey

AU - Fleischer, Norman

AU - Weir, Gordon

AU - Efrath, Shimon

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