A Stimulatory Effect of Tolbutamide on the Insulin-Mediated Glucose Uptake in Subjects with Impaired Glucose Tolerance (IGT)

Abstract

Several studies have indicated that the long-term effectiveness of sulfonylurea therapy in the treatment of type-II diabetics is due to a potentiation of insulin action. The present investigation was undertaken in order to elucidate whether or not there is also an acute effect of sulfonylureas on insulin-mediated glucose uptake. Nine non-obese subjects classified as having impaired glucose tolerance formed the study group. In vivo insulin sensitivity was assessed by using the glucose controlled insulin infusion system (Biostator) without or with a contemporary 3-hour tolbutamide infusion. Studies were performed on subsequent days, and each subject served as its own control. Glucose was given at a fixed rate of 0.011 mmol/kg b.w./min. The computer program was set to maintain plasma glucose concentration at 3.89 mmol/l. The amount of exogenous insulin necessary to keep glycemia at this steady-state level has been accepted as an estimate of insulin sensitivity. Mean plasma glucose and insulin concentrations were constant and comparable in control and sulfonylurea treated groups. Under our experimental conditions tolbutamide did not provoke any increase of C-peptide secretion. There was no significant alteration of insulin counterregulatory hormones (glucagon and growth hormone) either. On the other hand, for the disposal of identical quantities of glucose the necessary amount of insulin has been found to be reduced by one third due to tolbutamide treatment indicating a higher insulin sensitivity. The mechanism by which tolbutamide intensifies the insulin effect is unknown. It seems to be that a successful short-term sulfonylurea therapy on glucose utilization is associated with some alterations on the receptor and/or post-receptor level.

Pharmacokinetics and Biological Activity of the New Intermediate-Acting Insulin L-SNC1)

“…In order to exclude stimulation of endogenous insulin secretion in response to glucose infusion the C-peptide levels (HCP [Schulz et al, 1983]) were checked several times after insulin injection. Blood glucose concentrations were analyzed enzymatically (BIOSTATOR).…”