METFORMIN AMELIORATES DIABETES BUT DOES NOT NORMALIZE THE DECREASED GLUT-4 CONTENT IN SKELETAL-MUSCLE OF OBESE (FA FA) ZUCKER RATS

We studied the expression of the glucose transporter GLUT 4 in the sol eus and red gastrocnemius muscles from obese, diabetic (fa/fa) Zucker rats compared to their lean littermates (Fa/-), with and without treat ment with the antidiabetic drug metformin. In the untreated groups of rats, the GLUT 4 content in a crude membrane fraction of both the sole us and the red gastrocnemius muscles were significantly lower in the o bese (fa/fa) rats (3.46 +/- 0.28 vs. 6.04 +/- 0.41, p < 0.001 and 6.0 +/- 0.24 vs. 9.1 +/- 0.48, p < 0.0001, respectively). Differences in G LUT 4 expression in soleus muscle from the same rats were confirmed by quantitative immunofluorescence microscopy, and the results were sign ificantly correlated with the results obtained from quantitative immun oblotting (rho = 0.70, p < 0.0005). The decreased expression of GLUT 4 in fa/fa rats could contribute to the well-established insulin resist ance in skeletal muscle of these animals. After 4 weeks of treatment w ith metformin, weight gain was not affected in either the diabetic (fa /fa) rats or the lean (Fa/-) rats. Improvement of glucose homeostasis by metformin was not associated with normalization of the GLUT 4 expre ssion in the skeletal muscles studied, indicating (1) that the decreas ed GLUT 4 expression is not directly related to hyperinsulinaemia and diabetes mellitus and (2) that metformin does not normalize the expres sion of GLUT 4 in skeletal muscle of the diabetic (fa/fa) Zucker rats.