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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.

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