To investigate the hormonal and cellular selectivity of the prandial glucose regulators, we have undertaken a series of experiments, in which we characterised the effects of repaglinide and nateglinide on ATP-sensitive potassium ion (KATP) channel activity, membrane potential and exocytosis in rat pancreatic alpha-cells and somatotrophs. We found a pharmacological dissociation between the actions on KATP channels and exocytosis and suggest that compounds that, unlike repaglinide, have direct stimulatory effects on exocytosis in somatotrophs and alpha- and beta-cells, such as sulphonylureas and nateglinide, may have a clinically undesirable general stimulatory effect on cells within the endocrine system.