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 microM 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 Ca(2+)-sensitive, diacylglycerol-dependent protein kinase. These results suggest that Ca/CaM kinase II and MLCK may participate in the control of insulin release.
Niki
I
I
Department of Geriatrics, Nagoya University School of Medicine, Japan.
Okazaki
K
K
Saitoh
M
M
Niki
A
A
Niki
H
H
Tamagawa
T
T
Iguchi
A
A
Hidaka
H
H
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005576:Colforsin / Q000494:pharmacology; D015151:Immunoblotting; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009219:Myosin-Light-Chain Kinase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000096926:Benzenesulfonamides
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001381:Azepines; D001596:Benzylamines; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005576:Colforsin; D007328:Insulin; D007546:Isoquinolines; D009219:Myosin-Light-Chain Kinase; D009218:Myosins; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate; C056218:ML 9; C072105:KN 93; D000096926:Benzenesulfonamides; C063302:KN 62