Sulphonylurea receptor, type 1 <p>The sulphonylurea receptor (SUR) is a member of the ATP-binding cassettesuperfamily that associates with certain K⁺ channel inward rectifiersubunits to form ATP-sensitive K⁺ channels (KATP channels) [<cite idref="PUB00005203"/>, <cite idref="PUB00005208"/>]. These area family of K⁺ channels that are inhibited by intracellular ATP, which cancouple metabolic state to cell excitability. Their presence on pancreaticislet beta cells allows the cells to function as metabolic sensors,regulating insulin release in relation to glucose metabolism. Furthermore,SUR is the site of action for the sulphonylurea oral hypoglycaemic agentsthat are used widely for the treatment of non-insulin dependent diabetesmellitus. When these agents bind to the sulphonlyurea receptor, they reduceKATP channel activity, stimulating insulin release.</p><p>As mentioned, SUR is a member of the ATP-binding cassette superfamily(traffic adenosine triphsophatase superfamily), other members including theP-glycoprotein multi-drug resistance (MDR) proteins and the cysticfibrosis transconductance regulators (CFTRs). This raises the possibilitythat SUR may transport some endogenous substance, as yet unidentified.Two closely related genes have been found to encode the sulphonylureareceptors, SUR1 and SUR2, there being three splice variants of the secondform [<cite idref="PUB00005551"/>]. They are thought to contain 13-17 transmembrane (TM) domains,with two potential nucleotide binding folds, and a large number of possibleprotein kinase A, or C phosphorylation sites.</p><p>SUR1 is thought to be the sulphonylurea receptor isoform that is aconstituent of the pancreatic beta cell KATP channel. Several mutationshave been characterised in the human SUR1 gene, some of which are thoughtto be responsible for the rare inheritable metabolic disorder, familialpersistent hyperinsulinemic hypoglycemia of infancy, which is characterisedby excessive unregulated insulin secretion. SUR1 gene mutations may alsounderlie the varying sensitivity of some individuals to sulphonylureaoral hypoglycaemic agents [<cite idref="PUB00001106"/>].</p>