Effect of Age on Leucine-induced Insulin Secretion by the Cell

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Abstract
We have previously shown that aging is associated with a marked decrease in glucose-stimulated insulin release by the β-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 leucine or with 16.7 mM glucose. Islets from 12-month-old rats showed a decline in rate of leucine-induced insulin 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) μU/min/islet), respectively for 12-and 2-month-old rats. β-cell number is increased in islets from 12-month-old donors, and when this increase is taken into account, the average β3-cell from 12-month-old donors secretes only one-half the rate of β-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 β-cell function.