STIMULATORY EFFECT OF INSULIN ON CALCITONIN SECRETION

Infusion of insulin directly into thyroid arterial blood perfusing the surgically isolated in situ pig thyroid gland produced an increase in die secretion rate of calcitonin (CT) measured by immunoassay in thyr oid venous effluent blood. Insulin in concentrations ranging from appr oximately 1 to 400 ng/ml produced a maximal stimulation of 4-5 fold. T he stimulatory effect of insulin on CT could not be duplicated by infu sion of either IGF-I or amylin. Specific binding of radiolabeled insul in was demonstrated using isolated pig thyroid plasma membranes and bo th rat (6-23) and human (TT) medullary thyroid carcinoma C-cells. Incr eased CT release was observed from C-cells exposed to a high concentra tion of insulin. The administration of glucose iv to pigs in order to stimulate secretion of endogenous insulin produced an increase in circ ulating insulin. which was accompanied by an increase in the secretion of CT. The results show that insulin, delivered directly to the pig t hyroid gland, can stimulate CT release. The in vitro binding and secre tion studies indicate that C-cells can bind insulin and respond with a n increase in CT secretion, and the iv glucose experiments suggest tha t. endogenous insulin is capable of stimulating CT secretion. The find ings imply that insulin is capable of acting as a CT secretagogue and suggest that changes in CT secretion may accompany altered states of i nsulin production such as diabetes or insulin-secreting tumors.