REGULATION OF GLUCOSE-TRANSPORTER AND HEXOKINASE-II EXPRESSION IN TISSUES OF DIABETIC RATS

Glucose transport and phosphorylation are decreased in muscle and adip ose tissue in diabetes mellitus. The glucose transporter GLUT-4 and he xokinase II (HK II) are the main isoforms of proteins involved in gluc ose transport and phosphorylation in insulin-sensitive tissues, adipos e tissue, skeletal muscle, and heart. The molecular mechanisms respons ible for the decrease of glucose transport and phosphorylation have be en studied during the first 3 days after streptozotocin (STZ) administ ration in adult male Wistar rats. GLUT-4 mRNA and protein and HK II mR NA and enzyme activity were measured. After the injection of STZ (30 h ), GLUT-4 and HK II mRNAs were decreased to 10 +/- 1 and 20 +/- 3% tha t found in nondiabetic rats, respectively; they remained at these low levels for 72 h. Normalization of the blood glucose level by phlorizin infusion did not restore GLUT-4 and HK II mRNA concentrations to norm al. In contrast, normalization of the blood glucose level by physiolog ical infusion of insulin resulted in a total normalization of GLUT-4 a nd HK II mRNA concentrations. When insulin therapy was stopped, GLUT-4 and HK II mRNA and protein concentrations fell in 6 h to 40 and 20% o f control levels, respectively. Minimal changes of GLUT-4 and HK II mR NA, and of HK II activity, were observed in skeletal muscle and heart of diabetic rats. We conclude that GLUT-4 and HK II mRNA are coordinat ely expressed in white adipose tissue. They are rapidly affected by an acute decrease of the plasma insulin concentrations but are not modif ied by hyperglycemia. In contrast, skeletal muscle and heart GLUT-4 an d HK II mRNA are not greatly affected by short-term diabetes.