Overexpression of GLUT5 in diabetic muscle is reversed by pioglitazone.

OBJECTIVE This study was undertaken to quantify the expression of muscle GLUT in type 2 diabetes and to determine if treatment with an insulin-enhancing thiazolidenedione drug, pioglitazone, would alter its expression. RESEARCH DESIGN AND METHODS Twelve patients with type 2 diabetes were randomly assigned to treatment with either pioglitazone or placebo in a double-blinded 8-week protocol. Protein and mRNA for GLUT4 and GLUT5 were quantified in muscle homogenates from biopsies of vastus lateralis before and after treatment. The five additional GLUT family isoforms expressed in muscle had mRNA quantified in these samples. RESULTS Baseline and posttreatment repeat measurements of GLUT4 protein were not different from control measurements. Compared with normal subjects, GLUT5 protein increased 2.5-fold, and GLUT5 mRNA was 82% higher in the pretreatment samples from the diabetic subjects. Concentrations of mRNA for the six other GLUTs (GLUT1, GLUT3, GLUT4, GLUT8, GLUT11, and GLUT12) were not different from control subjects before or after treatment. The proportion of type I (red) fibers (46%) in diabetic muscle was not affected by pioglitazone treatment. Pioglitazone treatment decreased muscle GLUT5 mRNA and protein by 52 and 40%, respectively, whereas placebo did not alter GLUT5 expression. Both red and white fibers had higher GLUT5 expression in the baseline diabetic muscle samples, and a pioglitazone-related decrease in GLUT5 protein also occurred in both. CONCLUSIONS GLUT5 was dramatically increased in diabetic muscle, and pioglitazone treatment reversed this overexpression. The role of this fructose transporter expression in the insulin-enhancing effect of pioglitazone in muscle is unclear.