Proportional inhibition of glucose-induced insulin release by somatostatin

To test the hypothesis that somatostatin is a proportional inhibitor of glucose-induced insulin release, we examined the effect of somatostatin on the release of insulin stimulated either by endogenous signals (basal), by glucose infusion, or by glucose injection. Somatostatin infusions (1.7 micrograms/min x 30 min) produced a decrement of basal insulin output from the right lobe of the canine pancreas that was proportional to the initial rate of basal insulin secretion (r = -0.87, p < 0.001, n = 16). Glucose infusions of 1-6 mg/kg/min produced much higher rates of insulin output; again, the decrement of insulin output produced by somatostatin correlated with the initial rate of insulin secretion (r = -0.68, p < 0.01, n = 16). Rapid intravenous injection of either 2 or 20 g of glucose produced a wide range of acute insulin responses (AIR). Somatostatin produced a decrement that was proportional to the original magnitude of the AIR (r = -0.70, p < 0.005, n = 16). Thus, the absolute amount of inhibition produced by somatostatin increases, not decreases, with the magnitude of the stimulus. These data suggest that the inhibitory effect of somatostatin cannot be overcome by increasing the size of glucose stimulus. Thus, exogenous somatostatin, and presumably endogenous somatostatin as well, will produce an inhibitory effect at any physiologic level of glucose stimulation than the beta-cell receives.