Impaired glucose-stimulated insulin secretion and reduced -cell mass in pancreatic islets of hyperthyroid rats

摘要

To clarify the mechanism underlying the effect of thyroid hormone excess on pancreatic insulin secretion and abnormal glucose tolerance induced by hyperthyroidism, we investigated the effect of hyperthyroidism on the pancreatic -cell mass and two key components of the insulin secretory pathway, ATP-sensitive K+ (K-ATP) and L-type Ca2+ channels. In control and levothyroxine-treated hyperthyroid rats, an intraperitoneal glucose tolerance test was performed, and the insulin secretion and content of the isolated islets were assayed. In order to determine the effect of hyperthyroidism on K-ATP and L-type Ca2+ channels, isolated islets were exposed to specific pharmacological agents, including glibenclamide (K-ATP channel blocker), diazoxide (K-ATP channel opener) and nifedipine (L-type Ca2+ channel blocker). Histomorphometric changes and histochemistry of the islet in both groups were compared. Our data indicated that plasma glucose and insulin concentrations during the intraperitoneal glucose tolerance test in the hyperthyroid group were, respectively, higher and lower than in the control group. Insulin secretion and content of the hyperthyroid islets were reduced. The response of hyperthyroid islets to glibenclamide, diazoxide and nifedipine and the percentage change in insulin secretion were lower than those of the control islets. Despite the increase in weight and total volume of the pancreas, the volume of the islets and the total number of insulin-positive cells in hyperthyroid rats were reduced. Our data indicated that reduced insulin secretion in the hyperthyroid group might arise from reduced -cell mass and an abnormality in some parts of the insulin secretory pathway, including K-ATP and L-type Ca2+ channel function.