EVIDENCE FOR POSTTRANSCRIPTIONAL REGULATION OF GLUT4 EXPRESSION IN MUSCLE AND ADIPOSE-TISSUE FROM STREPTOZOTOCIN-INDUCED DIABETIC AND BENFLUOREX-TREATED RATS

In this study we explored the expression of GLUT4 glucose carriers in muscle and adipose tissues from streptozotocin-induced diabetic and be nfluorex-treated rats. In nondiabetic rats, benfluorex treatment decre ased GLUT4 protein content in muscle and brown adipose tissue, with no change in GLUT4 mRNA. This effect occurred in the presence of normal circulating levels of insulin and glucose. Seventeen days after strept ozotocin injection, diabetic rats showed a decreased GLUT4 protein con tent in adipose tissues and in both red and white skeletal muscle. Dia betic rats showed decreased GLUT4 mRNA levels in white and brown adipo se tissue, whereas messenger concentrations remained unaltered in red and white fibers of skeletal muscle. The interaction of benfluorex and diabetes on GLUT4 protein expression showed a tissue-specific pattern . Benfluorex treatment to some extent prevented the decrease in GLUT4 protein in white and brown adipose tissue and in white muscle associat ed with diabetes. In contrast, diabetes and benfluorex caused an addit ive decrease in GLUT4 expression in red skeletal muscle. The effects o f benfluorex on GLUT4 content in tissues from diabetic rats occurred i n the absence of alterations in GLUT4 mRNA levels, suggesting a modifi cation of translational or posttranslational steps. Benfluorex did not ameliorate the hyperglycemia of diabetic rats. Our results indicate t hat red and white skeletal muscle respond to diabetes and benfluorex i n a heterogeneous manner, which suggests the existence of differences in the mechanisms that regulate GLUT4 expression. Furthermore, our dat a indicate that GLUT4 expression in muscle and adipose tissue can be r egulated by modification of translational or posttranslational steps. Copyright (C) 1996 Elsevier Science Inc.