NEW PERSPECTIVES ON THE ACTIONS OF SULPHONYLUREAS AND HYPERGLYCEMIC SULFONAMIDES ON THE PANCREATIC B-CELL

Sulphonylureas and the hyperglycaemic sulphonamide diazoxide are commo nly employed in the therapy of non-insulin-dependent (Type 2) diabetes mellitus and insulinoma, respectively. Stimulatory effects of sulphon ylureas on insulin secretion and the inhibitory action of diazoxide ar e thought to be primarily mediated through modulation of the activity of ATP-sensitive K+ channels (K+-ATP channels) in the beta-cell plasma membrane. Certain sulphonylureas are known to be internalised by the pancreatic B-cell. Recent studies suggest that these drugs and diazoxi de can influence insulin secretion from electropermeabilised beta-cell s in which K+-ATP channels and other plasma membrane ion channels are inoperative. This observation suggests that sulphonylureas and diazoxi de interact with intracellular sites in the pancreatic B-cell which ar e directly involved in the regulation of the final stages of exocytosi s.