Defect in insulin action on expression of the muscle/adipose tissue glucose transporter gene in skeletal muscle of type 1 diabetic patients

Hannele Yki-Järvinen, Helena Vuorinen-Markkola, Laszlo Koranyi, Ray Bourey, Karen Tordjman, Mike Mueckler, Alan M. Permutt, Veikko A. Koivisto

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22 Scopus citations

Abstract

Recently several members of the glucose transporter family have been identified by molecular cloning techniques. We determined the effect of a 4-h insulin infusion on the expression of the muscle/adipose tissue (GLUT-4) glucose transporter mRNA and protein in 14 insulin-treated type 1 diabetic patients and 15 matched nondiabetic subjects. GLUT-4 mRNA and protein concentrations were determined in muscle biopsies taken before and at the end of the insulin infusion during maintenance of normoglycemia. In response to insulin, muscle GLUT-4 mRNA increased in the nondiabetic subjects from 24 ± 3 to 36 ± 4 pg/μg RNA (P < 0.001) but remained unchanged in the insulin-resistant diabetic patients (24 ± 2 vs. 26 ± 2 pg/μg RNA, before vs. after insulin). The glucose transporter protein concentrations were similar in the basal state and decreased by 21 ± 7% (P < 0.02) in the normal subjects but remained unchanged in the diabetic patients. The increase of the GLUT-4 mRNA and the decrease in the GLUT-4 protein correlated with the rate of glucose uptake [correlation coefficient (r) = -0.55, P < 0.01, and r = -0.44, P < 0.05, respectively]. We conclude that the insulin response of both the GLUT-4 glucose transporter mRNA and protein are absent in skeletal muscle of insulin-resistant type 1 diabetic patients. Thus, impaired insulin regulation of glucose transporter gene expression can be one of the underlying mechanisms of insulin resistance in type 1 diabetes.

Original languageEnglish
Pages (from-to)795-799
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume75
Issue number3
StatePublished - Sep 1992

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