1. The effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin were investigated in the isolated, incubated soleus muscle of the rat. 2. Hypothyroidism, which was induced by administration of propylthiouracil to the rats, decreased fasting plasma levels of free fatty acids and increased plasma levels of glucose but did not significantly change plasma levels of insulin. 3. The sensitivity of the rates of glycogen synthesis to insulin was increased at physiological, but decreased at supraphysiological, concentrations of insulin. 4. The rates of glycolysis in the hypothyroid muscles were decreased at all insulin concentrations studied and the EC50 for insulin was increased more than 8-fold; the latter indicates decreased sensitivity of this process to insulin. However, at physiological concentrations of insulin, the rates of glucose phosphorylation in the soleus muscles of hypothyroid rats were not different from controls. This suggests that hypothyroidism affects glucose metabolism in muscle not by affecting glucose transport but by decreasing the rate of glucose 6-phosphate conversion to lactate and increasing the rate of conversion of glucose 6-phosphate to glycogen. 5. The rates of glucose oxidation were decreased in the hypothyroid muscles at all insulin concentrations.
INTRODUCTIONPrevious studies have suggested that thyroid hormones influence the effect of insulin on the rate of glucose metabolism: in hyperthyroidism, the sensitivity of the rate of glucose production to insulin is decreased [1][2][3][4][5][6] whereas that of glucose uptake by skeletal muscle is increased [4,7]; in hypothyroidism, the rate of glucose production from the liver is decreased [8][9][10][11]. However, the effects of hypothyroidism on the sensitivity and responsiveness of glucose utilization to insulin have not been systematically studied. In hypothyroid patients, after administration of either intravenous glucose or insulin, and in the perfused rat hindquarter, the rate of utilization of glucose is either normal or decreased [11][12][13][14][15][16]. The effects of insulin on glucose utilization in isolated adipocytes from hypothyroid patients or rats are variable: the rate of glucose utilization is reported to be normal, decreased or increased [17][18][19]. The effects of insulin on glucose utilization in skeletal muscle have been investigated in only one study: markedly decreased rates of glycolysis and glycogen synthesis in soleus muscles isolated from hypothyroid rats were reported [19]. However, these experiments were performed in the presence of supraphysiological concentrations of insulin. The glycogen content is increased in soleus muscles isolated from hypothyroid rats [20,21] and it is normal in skeletal muscle of hypothyroid patients [22,23] which does not suggest that hypothyroidism should markedly decrease the sensitivity of the rate of this process to insulin. In view of the variability of the results in the above studies, it was decided to investigate the sensitivity of glucose u...