Suppression of Glucagon Secretion during a Tolbutamide Infusion in Normal and Noninsulin-Dependent Diabetic Subjects*

Publisher Website
Google Scholar
Abstract
To determine the effect of tolbutamide on glucagon release in noninsulin-dependent diabetic and normal subjects and how plasma glucose levels may modulate this effect, the acute glucagon response (AGR) to a 5-g iv arginine pulse was determined before and during a tolbutamide infusion. There was a decrease in plasma glucose concentration in both normal and diabetic subjects (both P < 0.001); there tended to be a suppression of the AGR (4 of 6 normals and 8 of 11 diabetics), but this suppression was not statistically significant. In separate studies, when the plasma glucose level was clamped at baseline values by a variable rate of glucose infusion, the AGR was suppressed during the tolbutamide infusion in all 7 normal [change in AGR (AAGR) = −35 ± 12 pg/ml; P < 0.05] and all 6 noninsulin-dependent diabetic subjects (AAGR = −14% 5 pg/ ml, p < .05). In 6 insulin-dependent diabetic subjects, there was no evidence of glucagon suppression by tolbutamide (AAGR = +2 ± 2 pg/ml). These results are consistent with the hypothesis that sulfonylureas suppress glucagon secretion by augmenting insulin secretion, an effect that falling glucose levels can mask. Consideration of this observation is necessary when interpreting the effects of a sulfonylurea on islet cell responses.(J Clin Endocrinol Metab56: 586, 1983)