Pr. Flatt et al., NEW PERSPECTIVES ON THE ACTIONS OF SULPHONYLUREAS AND HYPERGLYCEMIC SULFONAMIDES ON THE PANCREATIC B-CELL, Diabete et metabolisme, 20(2), 1994, pp. 157-162
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.