Extrapancreatic effects of hypoglycemic sulfonylureas: still a controversial issue

Abstract Sulfonylurea derivatives lower blood glucose by stimulating insulin release. In addition, they have been found to exert insulin-like effects, to enhance insulin action, and to augment insulin receptors. However, as Hans-Georg Joost explains, it is not unanimously accepted that these so-called extrapancreatic effects significantly contribute to the hypoglycemic action in the therapy of diabetes. Attempts to demonstrate a beneficial effect in insulin-dependent (type I) diabetes have failed. There is firm evidence that the receptor augmentation reflects improved glycemic control rather than a direct effect of the sulfonylureas. Although enhancement of insulin action has been clearly demonstrated in tissue culture, it is questionable whether the concentrations applied in vitro are achieved in vivo with therapeutic dosage.