THE EFFECTS OF INSULIN ON TRANSPORT AND METABOLISM OF GLUCOSE IN SKELETAL-MUSCLE FROM HYPERTHYROID AND HYPOTHYROID RATS

The effects of insulin on the rates of glucose disposal were studied i n soleus muscles isolated from hyper- or hypothyroid rats. Treatment w ith triiodothyronine for 5 or 10 days decreased the sensitivity of gly cogen synthesis but increased the sensitivity of lactate formation to insulin. The sensitivity of 3-O methylglucose to insulin was increased only after 10 days of treatment and was accompanied by an increase in the sensitivity of 2-deoxyglucose phosphorylation; however, 2-deoxygl ucose and glucose 6-phosphate in response to insulin remained unaltere d. In hypothyroidism, insulin-stimulated rates of 3-O-methylglucose tr ansport and 2-deoxyglucose phosphorylation were decreased; however, at basal levels of insulin, 3-O-methylglucose transport was increased, w hile 2-deoxyglucose phosphorylation was normal. In these muscles, the sensitivity of lactate formation to insulin was decreased; this defect was improved after incubation of the muscles with prostaglandin E-2. The results suggest: (a) in hyperthyroidism, insulin-stimulated rates of glucose utilization in muscle to form lactate are increased mainly because of a decrease in glycogen synthesis; when hypethyroidism progr esses in severity, increases in the sensitivity of glucose transport t o insulin and in the activity of hexokinase may also be involved; (b) in hypothyroidism, the decrease in insulin-stimulated rates of glucose utilization is caused by decreased rates of glycolysis; (c) prostagla ndins may be involved in the changes in sensitivity of glucose utiliza tion to insulin observed in muscle in altered thyroid states.