title: Molecular action of sulphonylureas on KATP channels: a real partnership between drugs and nucleotides.
abstract: Sulphonylureas stimulate insulin secretion from pancreatic β-cells primarily by closing ATP-sensitive K(+) channels in the β-cell plasma membrane. The mechanism of channel inhibition by these drugs is unusually complex. As direct inhibitors of channel activity, sulphonylureas act only as partial antagonists at therapeutic concentrations. However, they also exert an additional indirect inhibitory effect via modulation of nucleotide-dependent channel gating. In this review, we summarize current knowledge and recent advances in our understanding of the molecular mechanism of action of these drugs.
authors.affiliation: Department of Physiology, Anatomy and Genetics, Le Gros Clark building, University of Oxford, South Parks Road, Oxford OX1 3QX, England, U.K.
authors.forename: Heidi
authors.initials: H
authors.lastname: de Wet
authors.affiliation: Department of Physiology, Anatomy and Genetics, Le Gros Clark building, University of Oxford, South Parks Road, Oxford OX1 3QX, England, U.K. peter.proks@dpag.ox.ac.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: Proks
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D015640:Ion Channel Gating / Q000187:drug effects*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D054086:KATP Channels / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
chemical_list: D007328:Insulin; D054086:KATP Channels; D013453:Sulfonylurea Compounds; D000255:Adenosine Triphosphate
keywords: ABCC8; KATP channels; Kir6.2; SUR1; diabetes