Insulin Responses to Nonglucose Stimuli in Non-insulin-dependent Diabetes Mellitus During a Tolbutamide Infusion

To determine the effect of tolbutamide on insulin release to nonglucose stimuli in non-insulin-dependent diabetes mellitus and how plasma glucose levels may modulate this effect, the acute insulin response (AIR) to an isoproterenol (12 μg) or an arginine (5 g) i.v. pulse was determined before and during a tolbutamide infusion (7.5 mg/m²/min) in 25 male subjects. During the tolbutamide infusion, there was an increase in the AIR to both isoproterenol (% Δ AIR = +49 ± 21%, N = 11, P < 0.05) and arginine (% Δ AIR = +52 ± 15%, N = 12, P < 0.005) and a decrease in plasma glucose (Δ plasma glucose for isoproterenol = −24 ± 6 mg/dl, P < 0.005; for arginine = −26 ± 3 mg/dl, P < 0.001). In separate studies, when the plasma glucose was clamped at baseline values by a variable rate of glucose infusion, there was a greater effect of tolbutamide on AIR when compared with the unclamped tolbutamide studies (isoproterenol: % Δ AIR = +132 ± 25%, P < 0.025; arginine: % Δ AIR = +95 ± 12%, P < 0.05). Thus, tolbutamide increases the AIR of nonglucose stimuli, but this augmentation by tolbutamide is blunted by the concomitant decrease in plasma glucose. Consideration of this observation is necessary when interpretating the effects of a sulfonylurea on islet cell responses.