title: Underexpression of beta cell high Km glucose transporters in noninsulin-dependent diabetes.
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.
authors.affiliation: Center for Diabetes Research, University of Texas, Dallas 75235.
authors.forename: J H
authors.initials: JH
authors.lastname: Johnson
authors.forename: A
authors.initials: A
authors.lastname: Ogawa
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Orci
authors.forename: C B
authors.initials: CB
authors.lastname: Newgard
authors.forename: T
authors.initials: T
authors.lastname: Alam
authors.forename: R H
authors.initials: RH
authors.lastname: Unger
mesh_terms: D019325:3-O-Methylglucose; D000818:Animals; D001692:Biological Transport; D003920:Diabetes Mellitus / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000494:pharmacology; D015151:Immunoblotting; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism; D009765:Obesity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011924:Rats, Zucker
chemical_list: D007328:Insulin; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D019325:3-O-Methylglucose; D005947:Glucose