ATP-sensitive potassium channel regulatory subunit 1 (SUR1) (SUR1)

The ATP-sensitive potassium channel regulatory subunit 1 (SUR1), encoded by the ABCC8 gene, is a critical component of the KATP channel complex in pancreatic beta cells. It functions as a metabolic sensor by coupling the intracellular ATP/ADP ratio to the cell's membrane potential (UniProt P59941). When blood glucose levels rise, the resulting increase in ATP leads to KATP channel closure via SUR1, triggering membrane depolarization and subsequent insulin secretion (PubMed: 10592334). Mutations in the ABCC8 gene are associated with significant glycemic disorders, including congenital hyperinsulinism (loss-of-function) and neonatal diabetes (gain-of-function) (StatPearls: NBK537231). Pharmacologically, SUR1 is the primary target for sulfonylureas and glinides, which are used to treat type 2 diabetes by stimulating insulin release (PubChem: CID 3488). Additionally, KATP channel openers like diazoxide target SUR1 to suppress insulin release in conditions of hyperinsulinism (PubMed: 29073318). Beyond the pancreas, SUR1 is also expressed in certain neurons and atrial tissues, which may contribute to the side effect profile of drugs targeting this subunit (PubMed: 18403473).

Other names

Sulfonylurea receptor 1ABCC8ATP-binding cassette sub-family C member 8ABC36HHF1PHHIHIHRINSMRP8

Sulfonylureas and meglitinides act as KATP channel blockers by binding to the SUR1 subunit, which induces channel closure, membrane depolarization, and insulin release. Conversely, KATP channel openers like diazoxide act as KATP channel openers by binding to SUR1, hyperpolarizing the beta cell and inhibiting insulin secretion.