The effect of age and glucose concentration on insulin secretion by the isolated perfused rat pancreas.

Age changes in the beta-cell's sensitivity to glucose as well as in its overall capacity to secrete insulin may play a part in the glucose intolerance of aging. The isolated perfused rat pancreas preparation was used to study the effect of age and glucose level on insulin secretion. Overnight-fasted male Wistar 12- and 23-month-old rats had basal plasma glucose levels of 106 +/- 4 (SE) and 100 +/- 4 mg/dl. Perfusate glucose levels were raised from 80 mg/dl to either 150, 220, or 360 mg/dl for 50 min (n = 6 to 8 in each group). Insulin secretion followed the typical biphasic pattern of an early spike and fall, followed by a sustained gradual increase at both ages. First-phase (0-10 min) insulin secretion in the old rats was significantly lower at 150 (184 vs. 524 microU/min, P less than 0.05) and 220 mg/dl (327 vs. 644 microU/min, P less than 0.05), while it was nearly identical at 360 mg/dl. Although lower in the old rats, second-phase (11-50 min) insulin secretion was not statistically significantly different for each glucose level. When first- and second-phase insulin secretion rates were combined, the old rats' insulin secretion was only lower at the 150 mg/dl level (248 vs. 426 microU/min, P less than 0.05). Thus, at the more physiological glucose level, old rats showed a significantly lower response, while at the higher levels insulin secretion was similar. This diminishing age effect with increasing glucose dose suggests a defect in islet sensitivity to glucose rather than a diminished capacity to secrete insulin.