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

Sulphonylureas and the hyperglycaemic sulphonamide diazoxide are commonly employed in the therapy of non-insulin-dependent (Type 2) diabetes mellitus and insulinoma, respectively. Stimulatory effects of sulphonylureas on insulin secretion and the inhibitory action of diazoxide are 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 diazoxide can influence insulin secretion from electropermeabilised beta-cells in which K+-ATP channels and other plasma membrane ion channels are inoperative. This observation suggests that sulphonylureas and diazoxide interact with intracellular sites in the pancreatic B-cell which are directly involved in the regulation of the final stages of exocytosis.