The Effect of Age and Glucose Concentration on Insulin Secretion by the Isolated Perfused Rat Pancreas*

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Abstract
Age changes in the .beta.-cell 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-mo. old rats had basal plasma glucose levels of 106 .+-. (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 = 6-8 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 .mu.U/min, P < 0.05) and 220 mg/dl (327 vs. 644 .mu.U/min, P < 0.05), while it was nearly identical at 360 mg/dl. Although lower in the old rats, 2nd-phase (11-50 min) insulin secretion was not statistically significantly different for each glucose level. When 1st- and 2nd-phase insulin secretion rates were combined, the old rats'' insulin secretion was only lower at the 150 mg/dl level (248 vs. 426 .mu.U/min, P < 0.05). 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.