PRESENCE AND POSSIBLE INVOLVEMENT OF CA/CALMODULIN-DEPENDENT PROTEIN-KINASES IN INSULIN RELEASE FROM THE RAT PANCREATIC BETA-CELL

Roles of Ca/calmodulin-dependent protein kinase II (Ca/CaM kinase II) and myosin light chain kinase (MLCK) in insulin release from rat pancreatic islets were investigated. Western blotting using polyclonal antibody to Ca/CaM kinase II suggested the presence of this kinase in the pancreatic islets. Extracts of pancreatic islets phosphorylated exogenous myosin light chain, which was inhibited by ML-9, an inhibitor of MLCK. KN-62 and KN-93, inhibitors of Ca/CaM kinase II, and ML-9 at μM concentrations inhibited insulin release stimulated by glucose or high K+. KN-62 and KN-93, but not ML-9, inhibited insulin release increased by glucose and forskolin, an activator of adenylate cyclase. These inhibitors had no effect on insulin release evoked by 12-O-tetradecanoyl phorbol-13-acetate, an activator of Ca2+-sensitive, diacylglycerol-dependent protein kinase. These results suggest that Ca/CaM kinase II and MLCK may participate in the control of insulin release. © 1993 Academic Press. All rights reserved.