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Science 26 October 1990:
Vol. 250. no. 4980, pp. 546 - 549
DOI: 10.1126/science.2237405
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Articles

Science, Vol 250, Issue 4980, 546-549
Copyright © 1990 by American Association for the Advancement of Science

articles

Underexpression of beta cell high Km glucose transporters in noninsulin-dependent diabetes

JH Johnson, A Ogawa, L Chen, L Orci, CB Newgard, T Alam, and RH Unger

Center for Diabetes Research, University of Texas, Dallas 75235.

The role of defective glucose transport in the pathogenesis of noninsulin-dependent diabetes (NIDDM) was examined in Zucker diabetic fatty rats, a model of NIDDM. As in human NIDDM, insulin secretion was unresponsive to 20 mM glucose. Uptake of 3-O-methylglucose by islet cells was less than 19% of controls. The beta cell glucose transporter (GLUT-2) immunoreactivity and amount of GLUT-2 messenger RNA were profoundly reduced. Whenever fewer than 60% of beta cells were GLUT-2-positive, the response to glucose was absent and hyperglycemia exceeded 11 mM plasma glucose. We conclude that in NIDDM underexpression of GLUT-2 messenger RNA lowers high Km glucose transport in beta cells, and thereby impairs glucose-stimulated insulin secretion and prevents correction of hyperglycemia.


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