Presence and possible involvement of Ca/calmodulin-dependent protein kinases in insulin release from the rat pancreatic beta cell

Biochem Biophys Res Commun. 1993 Feb 26;191(1):255-61. doi: 10.1006/bbrc.1993.1210.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine* / analogs & derivatives*
  • Animals
  • Azepines / pharmacology
  • Benzylamines / pharmacology
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Colforsin / pharmacology
  • Immunoblotting
  • In Vitro Techniques
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / enzymology
  • Islets of Langerhans / metabolism*
  • Isoquinolines / pharmacology
  • Kinetics
  • Male
  • Myosin-Light-Chain Kinase / analysis
  • Myosin-Light-Chain Kinase / antagonists & inhibitors
  • Myosin-Light-Chain Kinase / metabolism*
  • Myosins / metabolism
  • Phosphates / metabolism
  • Phosphorus Radioisotopes
  • Piperazines / pharmacology
  • Protein Kinase Inhibitors
  • Protein Kinases / analysis
  • Protein Kinases / metabolism*
  • Rats
  • Rats, Wistar
  • Sulfonamides / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Azepines
  • Benzylamines
  • Insulin
  • Isoquinolines
  • Phosphates
  • Phosphorus Radioisotopes
  • Piperazines
  • Protein Kinase Inhibitors
  • Sulfonamides
  • ML 9
  • KN 93
  • Colforsin
  • KN 62
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Myosin-Light-Chain Kinase
  • Myosins
  • Tetradecanoylphorbol Acetate