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Overexpression of GLUT5 in Diabetic Muscle Is Reversed by Pioglitazone

¹Internal Medicine, East Tennessee State University, Quillen College of Medicine, Johnson City, Tennessee

stuartc{at}mail.etsu.edu

ABSTRACT

OBJECTIVE:: This study was undertaken to quantify the expression of muscle glucose transporters in type 2 diabetes and to determine if treatment with an insulin-enhancing thiazolidenedione drug, pioglitazone, would alter their 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 eight 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 post-treatment repeat of GLUT4 protein measurements were not different from controls. Compared to normal subjects, GLUT5 protein was increased 2.5-fold and GLUT5 mRNA was 82% higher in the pre-treatment samples from the diabetic subjects. Concentrations of mRNA for the six other glucose transporters (GLUT1, GLUT3, GLUT4, GLUT8, GLUT11, GLUT12) were not different from controls 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. Red and white fibers both had higher GLUT5 expression in the baseline diabetic muscle samples and the pioglitazone-related decrease in GLUT5 protein also occurred in both.

CONCLUSION:: 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.

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