Regulation of β-cell glucose transporter gene expression

Ling Chen, Tausif Alam, John H. Johnson, Steve Hughes, Christopher B. Newgard, Roger H Unger

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88 Scopus citations

Abstract

It has been postulated that a glucose transporter of β cells (GLUT-2) may be important in glucose-stimulated insulin secretion. To determine whether this transporter is constitutively expressed or regulated, we subjected conscious unrestrained Wistar rats to perturbations in glucose homeostasis and quantitated β-cell GLUT-2 mRNA by in situ hybridization. After 3 hr of hypoglycemia (glucose at 29 ± 5 mg/dl), GLUT-2 and proinsulin mRNA signal densities were reduced by 25% of the level in control rats. After 4 days (blood glucose at 57 ± 7 mg/dl vs. 120 ± 10 mg/dl in saline-infused control rats), GLUT-2 and proinsulin mRNA densities were reduced by 85% and 65%, respectively (P = 0.001). After 12 days (glucose at 54 ± 8 mg/dl) GLUT-2 mRNA signal density was undetectable whereas proinsulin mRNA was reduced by 51%. After 12 days of hypoglycemia, the K(m) for 3-O-methyl-D-glucose transport in isolated rat islets, normally 18-20 mM, was 2.5 mM. This provides functional evidence of a profound reduction of high K(m) glucose transporter in β cells. In contrast, GLUT-2 was only slightly reduced by hypoglycemia in liver. To determine the effect of prolonged hyperglycemia, we also infused animals with 50% (wt/vol) glucose for 5 days (glucose at 200 ± 50 mg/dl). Hyperglycemic clamping increased GLUT-2 mRNA by 46% (P = 0.001) whereas proinsulin mRNA doubled (P = 0.001). We conclude that GLUT-2 expression in β cells, but not liver, is subject to regulation by certain perturbations in blood glucose homeostasis.

Original languageEnglish (US)
Pages (from-to)4088-4092
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number11
DOIs
StatePublished - 1990

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