Molecular action of sulphonylureas on KATP channels: a real partnership between drugs and nucleotides

Biochem Soc Trans. 2015 Oct;43(5):901-7. doi: 10.1042/BST20150096.

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.

Keywords: ABCC8; KATP channels; Kir6.2; SUR1; diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / metabolism
  • Humans
  • Infant, Newborn
  • Insulin / metabolism
  • Insulin Secretion
  • Ion Channel Gating / drug effects*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • KATP Channels / metabolism*
  • Membrane Potentials / drug effects
  • Sulfonylurea Compounds / pharmacology*

Substances

  • Insulin
  • KATP Channels
  • Sulfonylurea Compounds
  • Adenosine Triphosphate