Investigations on the Antilipolytic Activity of Sulfonylureas in Man with Indications on Limit Dosages Concerning their Insulin-Secreting Properties

Abstract

In humans, estimations of the antilipolytic activities of sulfonylureas in in vivo experiments are difficult, because in addition to their antilipolytic activities the sulfonylureas have the more important property of provoking the release of insulin, which is itself antilipolytic. Therefore, studies of tolbutamide and glibenclamide in the range of lower limit dosages necessary for insulin secretion and blood glucose decrease were performed in healthy volunteers. Limit dosages causing increases of measurable peripheral insulin levels in humans after i.v. administration of glibenclamide and tolbutamide ranged from 0.001 to 0.005 mg/kg and from 0.1 to 1.0 mg/kg, respectively. With sulfonylurea concentrations below these limit dosages, antilipolytic activity can be observed without changes in peripheral blood glucose or peripheral insulin levels. These data suggest that the observed depression of FFA may be due to an antilipolytic effect of the sulfonylurea compounds, but the involvement of insulin could not be completely excluded.

Key words

Tolbutamide - Glibenclamide - Antilipolytic Activity - Limit Dosages

1 Present address: University of Massachusetts Medical School, Department of Biochemistry, Worcester, Massachusetts 01605, U.S.A.