Insulin secretory response to different secretagogues in hyper- and hypothyroid mice

The influence of long-term changes in thyroid state on insulin secretion was investigated in vivo in mice. Hyperthyroidism was induced by daily injections of L-triiodothyronine and hypothyroidism by a single injection of 131I. Four different insulin secretagogues were used to characterize the insulin secretory response, i.e. glucose, the beta 2-adrenoceptor agonist terbutaline, the cholinergic agonist carbachol and the synthetic C-terminal octapeptide of cholecystokinin, CCK-8. In the hyperthyroid mice the plasma glucose level was moderately decreased. Despite this lower glucose level the insulin response to terbutaline and glucose were potentiated by about 200%. Insulin response to CCK-8 and carbachol was less enhanced, by about 100 and 50%, respectively. Liver and muscle glycogen levels were markedly reduced. The hypothyroid animals showed reduced insulin responses to all secretagogues; after terbutaline by 100%, after carbachol by 70%, after glucose and CCK-8 by 50%. Plasma glucose and muscle glycogen levels were normal, whereas liver glycogen levels were moderately enchanced. Insulin release induced by beta-adrenoceptor stimulation was most markedly affected by the thyroid state, which thus may be of importance for the balance between the beta- and alpha-adrenoceptors of the insulin cell. Since thyroid activity influenced the insulin response to all secretagogues it cannot be excluded that the thyroid state also exerts effects not related to the adrenoceptors.