We have used the partially pancreatectomized infusion model in order to examine individual and combined effects of glucose and insulin on insulin resistance in rat skeletal muscles. Infusing glucose or insulin can produce animals which are hyperglycemic, hyperinsulinemic, or both. Individual and combined effects of chronic hyperglycemia and hyperinsulinemia on basal and insulin-mediated glucose utilization indices in glycolytic and oxidative muscle fibers were examined by 2-deoxyglucose uptake. Hyperglycemia reduced the basal glucose utilization index by 49% and hyperinsulinemia by 55%, while combined hyperglycemia + hyperinsulinemia diminished 2-deoxyglucose uptake by 69%. Maximally insulin-stimulated utilization was diminished only 28% under hyperglycemia but by 81% in the hyperinsulinemic state. In order to assess utilization in individual muscle fibers, uptake was examined in three tissues of differing fiber composition. The slow-twitch oxidative soleus muscle demonstrated greater basal uptake than the fast-twitch gastrocnemius (glycolytic) and quadriceps (oxidative) muscles. In addition basal (though not maximally insulin-stimulated) glucose utilization in the fast-twitch fibers was affected by chronic glucose and insulin to a greater extent than the slow-twitch soleus muscle, indicating that chronic hyperglycemia is more likely to precipitate insulin resistance in fast-twitch muscles. Significant differences in glucose metabolism among muscle fiber types suggests that results from insulin resistance studies in mixed muscles may be skewed according to their fiber composition.
Copyright 1998 Academic Press.