Sulphonylureas increase the number of insulin receptors

Abstract

SULPHONYLUREA drugs have been widely used in the management of the form of diabetes mellitus which develops in adulthood. Although some endogenous insulin secretory capacity seems to be necessary for Sulphonylureas to be effective (they are ineffective in pancreatectomised animals), their precise mechanism of action has not been clear. Short-term administration of Sulphonylureas to animals or humans is associated with increased insulin secretion^1,2. However, prolonged administration reduces pancreatic insulin content in animals^3,4 and diminished insulin secretion in reponse to nutrient stimulation in both laboratory animals⁵ and humans with adult-onset (insulin-independent) diabetes^6,7. Treatment with sulphonylureas also decreases the biosynthesis of proinsulin⁸. Thus, the chronic antidiabetic action of Sulphonylureas does not seem to result from an effect on insulin release, but rather from one or more extrapancreatic effects^9,10. In that connection, we have shown that chronic administration of the sulphonylurea, glipizide, to patients with adult-onset diabetes mellitus results in significant potentiation of insulin action, as assessed by changes in insulin-mediated glucose disposal¹¹. On the basis of those results, we have suggested that glipizide influences the interaction of insulin with the cell membranes in insulin-sensitive tissues. We now report that, in an animal model, such an effect involves an increase in the number of insulin receptors.