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

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/microgram RNA (P less than 0.001) but remained unchanged in the insulin-resistant diabetic patients (24 +/- 2 vs. 26 +/- 2 pg/microgram RNA, before vs. after insulin). The glucose transporter protein concentrations were similar in the basal state and decreased by 21 +/- 7% (P less than 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 less than 0.01, and r = -0.44, P less than 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.