Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3-O-Methylglucose
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Animals
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Biological Transport
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Diabetes Mellitus / metabolism
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Diabetes Mellitus, Experimental / metabolism*
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Diabetes Mellitus, Type 2 / metabolism*
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Female
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Gene Expression*
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Glucose / pharmacology
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Immunoblotting
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Insulin / metabolism
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Insulin Secretion
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Islets of Langerhans / drug effects
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Islets of Langerhans / metabolism*
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Kinetics
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Male
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Methylglucosides / metabolism
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Monosaccharide Transport Proteins / genetics*
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Monosaccharide Transport Proteins / metabolism
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Obesity
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RNA, Messenger / metabolism
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Rats
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Rats, Inbred Strains
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Rats, Zucker
Substances
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Insulin
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Methylglucosides
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Monosaccharide Transport Proteins
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RNA, Messenger
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3-O-Methylglucose
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Glucose