NEW MECHANISMS FOR SULFONYLUREA CONTROL OF INSULIN-SECRETION

Oral antidiabetic sulfonylureas like tolbutamide and glyburide have be en used to treat patients with noninsulin dependent diabetes mellitus. These agents lower blood glucose by stimulating insulin secretion fro m the pancreatic islets of Langerhans. A major component of this stimu lation is sulfonylurea-mediated closure of the ATP-inhibited potassium channels (K-ATP channels) of islet beta-cells, closure of these chann els leads to cell depolarization, calcium uptake, and insulin exocytos is. Progress leading up to the recent cloning of the high-affinity sul fonylurea receptor and reconstitution of the K-ATP channel is reviewed in this article together with new data showing that sulfonylureas may control secretion by activating a novel chloride ion channel, inhibit ing an islet Na/K/ATPase or via distal stimulation of granule exocytos is by a kinase C dependent mechanism.