ATP-binding cassette sub-family C member 8 (Sulfonylurea receptor 1) (SUR1)

ATP-binding cassette sub-family C member 8, commonly known as Sulfonylurea receptor 1 (SUR1), is a key regulatory subunit of the ATP-sensitive potassium (KATP) channel found in pancreatic beta-cells [1][3]. It assembles with the inward-rectifier potassium channel subunit Kir6.2 to form a hetero-octameric complex that acts as a metabolic sensor, linking the cell's metabolic state to its electrical activity [4]. When blood glucose levels rise, the resulting increase in the intracellular ATP/ADP ratio triggers the closure of these channels, leading to membrane depolarization and subsequent insulin secretion [5]. Dysregulation of this protein due to genetic mutations is a primary cause of disorders such as congenital hyperinsulinism and various forms of neonatal diabetes [1]. SUR1 is the pharmacological target for sulfonylureas and meglitinides, which promote insulin release in type 2 diabetes by inducing channel closure [2]. Conversely, channel openers like diazoxide are used to treat hyperinsulinemia by maintaining the channel in an open state, thereby inhibiting insulin exocytosis [4]. Sources: [1] UniProt Q09428; [2] StatPearls (Sulfonylureas); [3] NCBI Gene 6833; [4] Nature (2006) 440:440-448; [5] StatPearls (Physiology, Insulin).

Other names

ABCC8Sulfonylurea receptor 1SUR1MRP8PHHIHRINSABC36HHF1

Sulfonylureas and meglitinides bind to the SUR1 subunit of the KATP channel, causing the channel to close. This closure leads to membrane depolarization, opening of voltage-gated calcium channels, and subsequent insulin exocytosis [2][5]. Conversely, potassium channel openers like diazoxide bind to SUR1 to keep the channel open, inhibiting insulin secretion [1][4].