Sulfonylureas improve insulin binding and insulin action in non-insulin-dependent diabetes mellitus

Sulfonylureas reduce plasma glucose concentrations in most patients with non-insulin-dependent diabetes mellitus (NIDDM). The mechanism of this action is controversial. In this article we examine the issue of the peripheral effect of these drugs, i.e., the effect on insulin receptors and insulin action. In our studies we have found that sulfonylureas possess a selective regulatory in vivo effect on the cellular insulin binding to monocytes, independent of the diet and changes in plasma glucose and insulin concentrations. Furthermore, we found in in vitro studies that sulfonylureas affect the insulin receptors in a direct way. Thus, insulin binding to monocytes was increased during sulfonylurea treatment in both normal volunteers and patients with NIDDM. On the other hand, sulfonylureas seem to improve insulin action in NIDDM patients only. We conclude that the increased insulin binding in patients with NIDDM, induced by sulfonylurea treatment, may be of importance for the improved insulin action found in these patients. However, this hypothesis has to be proved.