EFFECTS OF HYPERINSULINEMIA ON MUSCLE-FIBER COMPOSITION AND CAPILLARIZATION IN RATS

Statistical studies repeatedly have shown an association between syste mic insulin resistance and a preponderance of highly glycolytic, relat ively insulin-insensitive muscle fibers as well as a low density of mu scle capillaries. The nature of the relationship between these observa tions is, however, not clear. Female rats were made hyperinsulinemic f or 7 days by implantation of osmotic minipumps. Elevated adrenergic ac tivity and secretion of glucocorticoids were controlled by another min ipump with propranolol and adrenalectomy was controlled with glucocort icoid substitution. This resulted in hyperinsulinemia and moderate hyp oglycemia, the latter probably counteracted by overeating and increase d glucagon secretion, as indicated by increased body weight and lower liver glycogen contents, respectively. Systemic insulin sensitivity wa s increased and measured with a hyperinsulinemic-euglycemic clamp tech nique. This was paralleled by an elevated glucose utilization estimate d as uptake of 2-deoxyglucose in parametrial, retroperitoneal, and ing uinal adipose tissues and the soleus and extensor digitorum longus mus cles. Glycogen synthesis was also elevated in the soleus muscle. Muscl e fiber composition changed with hyperinsulinemia and elevated 2-deoxy glucose uptake toward more fast-twitch, type II, particularly type IIb fibers, whereas the proportion of slow-twitch, type I fibers, diminis hed. Capillary density was elevated per unit muscle surface area as we ll as per muscle fiber. This was paralleled by increased insulin sensi tivity systemically and in muscles. These results suggest that muscle fiber composition alterations may be a consequence rather than a cause of hyperinsulinemia and that capillarization rather than fiber compos ition is of importance for insulin sensitivity in muscle.