Insulin Binding and its Action in Adipocytes of Hyperthyroid and Hypothyroid Rats

Abstract

The studies of the effects of thyroid hormone on insulin secretion and glucose metabolism have been made, but the results have been controversial.In order to evaluate the effects of thyroid hormone at the cellular level, insulin binding and insulin-induced lipogenesis in isolated rat epididymal fat cells were studied in control, hyperthyroid and hypothyroid rats. Hyperthyroidism was induced by daily intraperitoneal injection of sodium L-thyroxine and hypothyroidism by a single injection of 131I. The adipocytes were isolated by treatment of collagenase as originally described by Gliemann (1967).The results were as follows: 1) The fasting serum insulin levels of hyperthyroid (21.6 ± 3.7 uU/ml) and hypothyroid groups (20.5 ± 7.0 uU/ml) were not different from the value of control (23.1 ± 11 uU/ml). The fasting blood glucose level of hypothyroid group (164.9 ± 12.0 mg/dl) was higher than the values of the controls (148.2 ± 13.2 mg/dl) or the hyperthyroid group (147.0 ± 12.5 mg/dl), (p<.005).2) The specific 125I-insulin binding of the hyperthyroid group was not different from the value of the controls, but the value of the hypothyroid group was higher than the value of the controls (p<.005).3) The insulin receptor concentration of the hypothyroid group (1.09 ± 0.02 ng/0.5×105 cells) was higher than the value of the controls (0.72 ± 0.01 ng/0.5×105 cells) or the hyperthyroid group (0.79 ± 0.02 ng/0.5×105 cells), (p<.05).4) The average affinities of the receptors in all groups showed an inverse correlation with the insulin concentration. The average affinity of the hypothyroid group was higher than the value of the control or the hyperthyroid group.5) Insulin-induced lipogenesis was reduced proportionately in all insulin concentrations in both the hyperthyroid and hypothyroid groups compared with the dose-response curve of the control group. The maximal amount of lipogenesis of the hyperthyroid and hypothyroid groups were 63.4% (p<.05) and 32.3% (p<.005) of the controls, respectively.These studies suggest that thyroid hormone may regulate the concentration of insulin receptors, and altered thyroid states reduce insulin-induced lipogenesis in the adipocyte at postreceptor levels.