Effect of age on leucine-induced insulin secretion by the beta-cell.

We have previously shown that aging is associated with a marked decrease in glucose-stimulated insulin release by the beta-cell. To determine whether this age-related defect occurs with other insulin secretagogues, we have investigated leucine-stimulated insulin release. Islets of Langerhans were isolated from 2- and 12-month-old rats, and incubated with 5-20 mM 5-20 mM leucine or with 16.7 mM glucose. Islets from 12-month-old rats showed a decline in rate of leucine-induced secretion as compared to islets of 2-month-old donors (i.e., mean (+/- SEM) insulin secretion at 20 mM leucine was 0.79 (+/- 0.06) and 1.17 (+/- 0.09) microU/min/islet), respectively for 12- and 2-month-old rats. beta-cell number is increased in islets from 12-month-old donors, and when this increase is taken into account, the average beta-cell from 12-month-old donors secretes only one-half the rate of beta-cells from 2-month-old donors. These findings are comparable to those seen after glucose-stimulation, and emphasize the potential global nature of the age-related defect in beta-cell function.