An Insulin Dependent Effect of Chronic Tolbutamide Administration on the Skeletal Muscle Carbohydrate Transport System

Abstract

With the use of an in vitro intact mouse diaphragm preparation, the effects of tolbutamide on the sugar transport system of skeletal muscle as measured by 2 deoxyglucosc uptake (2-DG) was studied. Tolbutamide alone was found to have no effect on in vitro 2-DG uptake. Insulin mediated 2-DG uptake in vitro was not consistently changed by the addition of tolbutamide to the system. However, diaphragms from either subacute (24 hrs.) or chronically (eight to twelve days) tolbutamide treated animals showed a consistent increase in insulin mediated 2-DG uptake as compared to the appropriate controls. It was necessary to have tolbutamide in the preincubation and incubation medium in order to demonstrate this effect on the diaphragms of tolbutamide treated animals. This in vitro potentiation of insulin mediated 2-DG uptake occurred with physiologic concentrations of insulin (26 μU.'ml.) and normal therapeutic levels of tolbutamide (0.2 mg./ml.). The data suggest that potentiation of insulin action on the skeletal muscle sugar transport system maybe one of the major effects of tolbutamide therapy.