Publication Date:
1990-10-26
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, J H -- Ogawa, A -- Chen, L -- Orci, L -- Newgard, C B -- Alam, T -- Unger, R H -- DK02700-30/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1990 Oct 26;250(4980):546-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Diabetes Research, University of Texas, Dallas 75235.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2237405" target="_blank"〉PubMed〈/a〉
Keywords:
3-O-Methylglucose
;
Animals
;
Biological Transport
;
Diabetes Mellitus/metabolism
;
Diabetes Mellitus, Experimental/*metabolism
;
Diabetes Mellitus, Type 2/*metabolism
;
Female
;
*Gene Expression
;
Glucose/pharmacology
;
Immunoblotting
;
Insulin/secretion
;
Islets of Langerhans/drug effects/*metabolism
;
Kinetics
;
Male
;
Methylglucosides/metabolism
;
Monosaccharide Transport Proteins/*genetics/metabolism
;
Obesity
;
RNA, Messenger/metabolism
;
Rats
;
Rats, Inbred Strains
;
Rats, Zucker
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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