To determine how sulfonylureas affect beta cell function, insulin release in response to isoproterenol and arginine was assessed in 32 normal subjects before and during a tolbutamide infusion. When the plasma glucose was allowed to decrease during tolbutamide, the acute insulin response (AIR) to isoproterenol was not changed (AAIR = −4 ± 8 μU/ml, 
± SEM, n = 8, p = NS) and was enhanced slightly for arginine (ΔAIR = +61 ± 26 μU/ml, n = 6, p < 0.05). When plasma glucose levels were maintained by means of a concomitant variable glucose infusion during tolbutamide, the insulin responses to both isoproterenol and arginine were enhanced (isoproterenol: ΔAIR = +55 ± 15 μU/ml, n = 6, P < 0.001; arginine: ΔAIR = +137 ± 34 μU/ml, n = 8, P < 0.001). Regression analysis demonstrated a linear relationship between change in the prestimulus glucose level and the change in the AIR to isoproterenol during tolbutamide (r = 0.66, n = 14, P < 0.02). Since the slope of this relationship is not significantly different from a similar relationship in the absence of tolbutamide, the potentiating effect of tolbutamide is an amplification of an established physiologic relationship. We conclude that tolbutamide augments the insulin response to nonglucose stimuli. However, this potentiating effect of tolbutamide may be masked by a decrease in the prestimulus glucose level.
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