EFFECT OF AGE ON GLUCOSE-STIMULATED INSULIN RELEASE BY THE BETA-CELL OF THE RAT

To assess the effect of age on β-cell insulin release, collagenase-isolated islets of Langerhans were obtained from rats aged 2-18 mo and incubated with increasing concentrations of glucose. Similar islets were analyzed for insulin content or subjected to morphometric measurements to identify both the number of β-cells and the volume of β-granules per islet. In parallel studies, the islet content of intact pancreata was also determined. The results showed that β-cell number increased from 2,300 to 5,000 cells as rats aged from 2 to 18 mo and islet insulin content doubled. However, glucose-stimulated insulin release decreased progressively with age, and this was especially striking when considered in terms of the increase in number of β-cells/islet; e.g., mena (±SEM) insulin secretion (nanounits per minute per β-cell) of islets incubated with 450 mg/dl of glucose was 1.3 (±0.2), 1.0 (0.1), 0.4 (±0.05), and 0.3 (±0.01), respectively for 2-, 6-, 12-, and 18-mo-old rats. Thus, insulin secretion per β-cell was decreased, despite increased stores of insulin per cell. These findings demonstrate that the aging process leads to a profound defect in glucose-stimulated insulin release from the β-cell. Whether this is a global secretory defect, or solely a failure of the β-cell to respond to glucose, remains to be defined.