INSULIN-INDUCED TRANSLOCATION OF GLUT-4 IN SKELETAL-MUSCLE OF INSULIN-RESISTANT ZUCKER RATS

The genetically obese Zucker rat (fa/fa) is an animal model with sever e insulin resistance of the skeletal muscle. We investigated whether a defect of insulin-dependent glucose transporter (GLUT 4) translocatio n might contribute to the pathogenesis of the insulin-resistant state. fa/fa rats,lean controls (Fa/Fa) as well as normal Wistar rats were i njected intraperitoneally with insulin and were killed after 2 or 20 m in, respectively. Subcellular fractions were prepared from hind-limb s keletal muscle and were characterized by determination of marker-enzym e activities and immunoblotting applying antibodies against alpha 1 Na +/K+ AT Pase. The relative amounts of GLUT 1 and GLUT 4 were determine d in the fractions by immunoblotting with the respective antibodies. I nsulin induced an approximately two-fold increase of GLUT 4 in a plasm a membrane and transverse tubule enriched fraction and a decrease in t he low density enriched membrane fraction in all three groups of rats. There was a high individual variation in GLUT 4 translocation efficie ncy within the groups. However, no statistically significant differenc e was noted between the groups. No effect of insulin was detectable on the distribution of GLUT 1 or alpha 1 Na+K+ AT Pase. The data suggest that skeletal muscle insulin resistance of obese Zucker rats is not a ssociated with a lack of GLUT 4 translocation.