INSULIN-SECRETION BY THE PANCREATIC BETA-CELL OF AGED RATS

Insulin release by the pancreatic islets of 12-week- and 2-year-old male Wistar rats was compared using glucose and non-fuel secretagogues such as forskolin, phorbol ester (l2-O-tetradecanoylphorbol-13-acetate) and glyburide acting on adenylyl cyclase, C kinase, and the ATP-sensitive K+ channel, respectively. Sensitivity of the voltage-dependent calcium channel to nifedipine was also examined. In the beta cell of aged rats, the following abnormalities were found: (a) right shift of the dose-response curve (depressed sensitivity) of glucose-induced insulin release, (b) no increase of the maximum response to glucose in the face of increased insulin content of the islets (reduced responsiveness), (c) no response to forskolin and normal response to the phorbol ester and glyburide, and (d) increased sensitivity to nifedipine. In the beta cell of aged rats, sensitivity and responsiveness to glucose are depressed and cyclic AMP-dependent exocytosis and the calcium channel are abnormal.