Sulfonylurea receptor (SUR1)

Class

Sulfonylurea (insulin secretagogue)

The sulfonylurea receptor (SUR1) is a regulatory subunit of the ATP-sensitive potassium (KATP) channel found on the surface of pancreatic beta cells, the insulin-producing cells of the pancreas. Under normal physiology, glucose metabolism raises intracellular ATP, which closes KATP channels, depolarizes the cell membrane, and triggers calcium influx that causes insulin to be released. In type 2 diabetes, this glucose-sensing pathway becomes sluggish, and beta cells release insufficient insulin relative to blood glucose levels. Sulfonylureas bind directly to SUR1 and close the KATP channel independent of glucose sensing, forcing membrane depolarization and insulin secretion regardless of the ambient glucose concentration. This makes them effective at lowering blood glucose in patients who retain some functional beta cell mass, but because the mechanism does not respect glucose levels, it carries an inherent risk of driving glucose too low. SUR1 is part of a broader family of sulfonylurea receptor subunits found in other tissues, so drugs targeting this receptor are selected in part for how selectively they act on the pancreatic form. This mechanism remains one of the oldest and most established approaches to stimulating insulin release in diabetes management.