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

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Abstract
To understand the causes of the hyperglycemia 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-cAMP system was studied in isolated islets from 12 mo. old and 2 1/2 mo. 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 mo. old and 2 1/2 mo. 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 < 0.02) from islets of the older animals. Adenylate cyclase activity was diminished by 60% (P < 0.005) from the 12 mo. old rats as compared with islets from the 2 1/2 mo. old controls, while low Km phosphodiesterase activity was similar in islets from both groups of animals. The adenylate cyclase-cAMP system may play a role in the altered insulin release from islets of aging rats.