PKC-DEPENDENT STIMULATION OF EXOCYTOSIS BY SULFONYLUREAS IN PANCREATIC BETA-CELLS

Hypoglycemic sulfonylureas represent a group of clinically useful anti diabetic compounds that stimulate insulin secretion from pancreatic be ta cells. The molecular mechanisms involved are not fully understood b ut are believed to involve inhibition of potassium channels sensitive to adenosine triphosphate (K-ATP channels) in the beta cell membrane, causing membrane depolarization, calcium influx, and activation of the secretory machinery. In addition to these effects, sulfonylureas also promoted exocytosis by direct interaction with the secretory machiner y not involving closure of the plasma membrane K-ATP channels. This ef fect was dependent on protein kinase C (PKC) and was observed at thera peutic concentrations of sulfonylureas, which suggests that it contrib utes to their hypoglycemic action in diabetics.