Sulfonylurea sensitivity of adenosine triphosphate-sensitive potassium channels from β cells and extrapancreatic tissues

Sulfonylureas are widely used to stimulate insulin secretion in type 2 diabetic patients because they close adenosine triphosphate-sensitive potassium (K-ATP) channels in the pancreatic beta-cell membrane. This action is mediated by binding of the drug to the sulfonylurea receptor (SUR1) subunit of the channel. K-ATP channels are also present in a range of extrapancreatic tissues, but many of these contain an alternative type of SUR subunit (SUR2A in heart and SUR2B in smooth muscle). The sulfonylurea-sensitivity of K-ATP channels containing the different types of SUR is variable: gliclazide and tolbutamide block the beta cell, but not the cardiac or smooth muscle types of K-ATP channels with high affinity. Glibenclamide and glimepiride, on the other hand, block channels containing SUR1 and SUR2 with similar affinity. The reversibility of the different sulfonylureas also varies. Tolbutamide and gliclazide produce a reversible inhibition of Kir6.2/SUR1 and Kir6.2/SUR2 channels, whereas glibenclamide has a reversible effect on cardiac, but not beta-cell, K-ATP channels. In this article, we summarize current knowledge of how sulfonylureas act on K-ATP channels containing the different types of sulfonylurea receptor, and discuss the implications of these findings for the use of sulfonylureas in the treatment of diabetes mellitus, Copyright (C) 2000 by W.B. Saunders Company.