Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine* / analogs & derivatives*
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Animals
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Azepines / pharmacology
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Benzylamines / pharmacology
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Calcium-Calmodulin-Dependent Protein Kinases
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Colforsin / pharmacology
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Immunoblotting
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In Vitro Techniques
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Insulin / metabolism*
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Insulin Secretion
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Islets of Langerhans / drug effects
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Islets of Langerhans / enzymology
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Islets of Langerhans / metabolism*
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Isoquinolines / pharmacology
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Kinetics
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Male
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Myosin-Light-Chain Kinase / analysis
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Myosin-Light-Chain Kinase / antagonists & inhibitors
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Myosin-Light-Chain Kinase / metabolism*
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Myosins / metabolism
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Phosphates / metabolism
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Phosphorus Radioisotopes
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Piperazines / pharmacology
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Protein Kinase Inhibitors
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Protein Kinases / analysis
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Protein Kinases / metabolism*
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Rats
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Rats, Wistar
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Sulfonamides / pharmacology
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Tetradecanoylphorbol Acetate / pharmacology
Substances
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Azepines
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Benzylamines
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Insulin
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Isoquinolines
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Phosphates
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Phosphorus Radioisotopes
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Piperazines
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Protein Kinase Inhibitors
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Sulfonamides
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ML 9
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KN 93
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Colforsin
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KN 62
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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Protein Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Myosin-Light-Chain Kinase
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Myosins
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Tetradecanoylphorbol Acetate