THE EFFECTS OF LONG-TERM HYPERINSULINEMIA ON INSULIN SENSITIVITY IN RATS

The effects of long-term exposure (7 wk) to hyperinsulinaemia on insul in sensitivity were studied in female rats. The rats were made hyperin sulinaemic by implantation of osmotic minipumps that were changed once a week. Elevated adrenergic activity and secretion of glucocorticoids were controlled by another minipump with propranolol and adrenalectom y with corticosterone substitution, respectively. This resulted in hyp erinsulinaemia and moderate hypoglycaemia, the latter probably counter acted by overeating and increased glucagon secretion, as indicated by increased body weight and lower liver glycogen contents, respectively. Euglycaemic, hyperinsulinaemic clamp measurements showed a significan tly higher glucose disposal rate (P < 0.05) in the hyperinsulinaemic r ats 18.8 +/- 1.1 mg kg(-1) min(-1) compared with the control groups 14 .6 +/- 0.4 and 15.4 +/- 0.9 mg kg(-1) min(-1). insulin stimulation of 2-deoxyglucose as well as glycogen synthesis was measured in the exten sor digitorum longus muscle, the red and white part of the gastrocnemi us, the soleus muscle, the liver and in parametrial, retroperitoneal, and inguinal adipose tissue. No differences were found between the gro ups in the insulin response of the 2-deoxyglucose uptake. Glycogen syn thesis was significantly elevated in all muscles in the insulin treate d compared with the control rats but no differences were found in the liver. Capillary density was significantly elevated per unit muscle su rface area in the soleus and extensor digitorum longus muscles of the insulin-exposed rats. These results suggest that long-term exposure to insulin is followed by increased insulin sensitivity, apparently loca lized to the insulin regulation of glycogen synthesis in muscles. Musc le capillary density is elevated in parallel.