Role of the adenylate cyclase system in altered insulin release from islets of Langerhans of aging rats.

In attempting to understand the causes of the hyperglycaemia observed in aging populations and to determine the mechanism(s) for the diminished in vitro insulin release from islets of Langerhans of older rats, the adenylate cyclase-cyclic AMP system was studied in isolated islets from 12 month old and 2 1/2 month old (control) male rats to determine its role in this altered insulin secretion. Islets of Langerhans were isolated by collagenase digestion and then either incubated in the presence of low or high concentrations of glucose for studies of insulin release or were sonicated and assayed for determinations of activities of adenylate cyclase and phosphodiesterase. Insulin release was identical from islets of 12 month old and 2 1/2 month old rats to 2.8 mM D-glucose, while in the presence of 16.7 mM D-glucose, insulin release was decreased by 33% (P less than 0.02) from islets of the older animals. Adenylate cyclase activity was diminished by 60% (P less than 0.005) from the 12 month old rats as compared with islets from the 2 1/2 month old controls, while low Km phosphodiesterase activity was similar in islets from both groups of animals. From these studies it appears that the adenylate cyclase-cyclic AMP system may play a role in the altered insulin release from islets of aging rats.