Studies of secretin-stimulated insulin responses in man.

Recent studies have suggested that secretin, like glucose, stimulates a rapid insulin response from a small storage pool. In order to evaluate the mechanism of the secretin-stimulated insulin response, small (15 U) rapidly administered intravenous injections (pulses) of secretin were given before, during, and after a 20 hr 300 mg/min glucose infusion. Contrary to previous studies demonstrating that the acute insulin response to a small (5 g) pulse of glucose given 45 min after the start of the glucose infusion was significantly diminished compared to the response to the preinfusion pulse, the acute insulin response (2-5 min Deltaimmuno-reactive insulin muU/ml) to 15-U secretin pulses exhibited a greater than twofold increase (before: 31.1+/-15.4; during: 71.2+/-40.4, muU/ml, mean +/-SD, P < 0.02). The increased response to secretin was also found after 20 hr of continuous glucose infusion, but was not observed 1 hr after cessation of the infusion when plasma glucose levels returned to control values. Thus, this increased response to secretin was glucose dependent. Four 150-U secretin pulses given at 30 min intervals elicited progressively and significantly diminished acute insulin responses with each succeeding pulse, consistent with depletion of the small storage pool. Similar to the observation that the magnitude of the insulin response to secretin was glucose dependent, the glucose-stimulated output appeared to be secretin dependent. Thus the acute insulin response to 5 g glucose was increased after secretin pretreatment (presecretin: 34.9+/-14.8; postsecretin: 50.5+/-22.5 muU/ml. P < 0.02) which suggests that secretin may either enlarge the storage pool stimulated by glucose or increase its sensitivity. The effect of epinephrine and propranolol on acute insulin responses to secretin and glucose was also different. 15-U secretin pulses were unaffected by infusions of either epinephrine (pre: 31.6+/-17.9; during: 27.8+/-16.6 muU/ml) or propranolol (pre: 12.8+/-8.4; during: 10.7+/-5.5 muU/ml). The results of these studies indicate that although both glucose and secretin stimulate a rapid insulin response, these responses are easily differentiated. The data suggest that glucose and secretin stimulate functionally separate storage pools of insulin, but that the acute response to either stimulus is partly determined by exposure to the other.