Insulin Release in Aging: Studies on Adenylate Cyclase, Phosphodiesterase, and Protein Kinase in Isolated Islets of Langerhans of the Rat*

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Abstract
The enzymes of the adenylate cyclase-cAMPprotein phosphorylation system have been studied in islets of Langerhans from older and young male Sprague-Dawley rats to ascertain if changes in these enzymes might be related to the decreased insulin release observed from islets of aging rats and to the hyperglycemia of aging. Islets of Langerhans were isolated by collagenase digestion from pancreases of 15-month-old male Sprague-Dawley rats and 3-month-old male controls. The islets were incubated in Krebs- Ringer bicarbonate buffer with low or high concentrations of glucose for studies of insulin release or were sonicated and assayed for adenylate cyclase, high and low Km phosphodiesterase, and basal protein kinase activities. Basal insulin secretion with 2.8 DIM D-glucose was not different in the two groups of islets (22.3 ± 3.6 pg insulin released islet-1 min-1 from 15-month-old rats compared with 22.5 ± 3.3 from controls; P > 0.9). In response to 16.7 mM D-glucose, insulin release was diminished in islets from older rats by 33% relative to islets from controls (95 ± 4 pg insulin released islet-1 min-1 from older rats compared with 141 ± 6 from islets of the controls; P < 0.005). Basal adenylate cyclase activity was decreased by 57% in islets from 15-month-old rats compared with islets from the young rats (17.1 ± 3.5 pmol cAMP mg-1 min-1 in islets from older rats compared with 39.3 ± 4.6 from islets of 3-month-old rats; P < 0.005). High Km phosphodiesterase activity (15-montholdrats, 221 ± 12 pmol cAMP mg-1 min-1; 3-month-old rats, 228 ± 26; P < 0.7) and low Km phosphodiesterase activity (15-monthold rats, 7.7 ± 1.3 pmol cAMP mg-1 min-1; 3-month-old rats, 6.6 ± 0.8; P < 0.2) were unchanged. Basal protein kinase activity in islets from older rats was similar to that in controls (124 ± 16 pmol 32PC>4 mg-1 min-1 for older rats compared with 122 ± 13 from young controls; P < 0.8). From the results of these enzyme assays, it appears that the adenylate cyclase-cAMP system may play a significant role in the altered insulin release from islets of aging rats.