Effect of T₃ on Insulin Action, Insulin Binding, and Insulin Receptor Kinase Activity in Primary Cultures of Rat Hepatocytes

Summary

In vivo studies have demonstrated that the liver is the main site of insulin resistance in hyperthyroidism. To further investigate the effect of thyroid hormone in the liver, we have incubated primary cultures of rat hepatocytes in the presence and absence of triiodothyronine (T₃) 1 ng/ml and 5 ng/ml for 20 hr. Without affecting basal activity, T₃ 5 ng/ml decreased insulin-stimulated (1 × 10^-7M) lipid synthesis but not insulin-stimulated α-aminoisobutyric acid uptake. These changes occur in the absence of any abnormalities in ¹²⁵I-insulin binding, degradation, internalization or insulin receptors structure as determined by affinity-labeling methods. However, basal insulin receptor kinase activity using Glu4: Tyrl as phospho-acceptor was decreased by T₃ without altering its insulin responsiveness.

These results demonstrate the heterogeneity of T₃'s effects at the postinsulin binding level in the liver.

Key-Words

Thyroid Hormones - Insulin Action - Insulin Processing - Insulin Receptors - Insulin Receptor Kinase - Cultured Rat Hepatocytes