Selective block of K(ATP) channels: why the anti-diabetic sulphonylureas and rosiglitazone have more in common than we thought.

Rosiglitazone, the thiazolidinedione class anti-diabetic withdrawn from Europe in 2010 amid reports of adverse cardiovascular effects, is revealed by Yu et al. in this issue of the British Journal of Pharmacology to be a selective blocker of ATP-sensitive potassium (K(ATP) ) channels. This seems little cause for excitement given that the closure of pancreatic K(ATP) channels is integral to insulin secretion; and sulphonylureas, which inhibit K(ATP) channels, are widely used to treat type II diabetes. However, rosiglitazone, whose primary targets are nuclear transcription factors that regulate genes involved in lipid metabolism, blocks K(ATP) channels by a novel mechanism different to that of the sulphonylureas and has a worrying preference for blood flow-regulating vascular K(ATP) channels. Identification of a new molecule that modulates K(ATP) channel gating will not only tell us more about how these complex metabolic sensors work but also raises questions as to whether rosiglitazone suppresses the cardiovascular system's ability to cope with metabolic stress - a claim that has dogged the sulphonylureas for many years.