Involvement of protein kinase C-epsilon in inositol hexakisphosphate-induced exocytosis in mouse pancreatic beta-cells

J Biol Chem. 2003 Sep 12;278(37):35168-71. doi: 10.1074/jbc.M303927200. Epub 2003 Jul 1.


Inositolhexakisphosphate (InsP6) plays a pivotal role in the pancreatic beta-cell stimulus-secretion coupling. We have used capacitance measurements to study the effects of InsP6 on Ca2+-dependent exocytosis in single mouse pancreatic beta-cells. In the presence of inhibitors of the protein phosphatase calcineurin to block endocytosis, intracellular application of InsP6 produced a dose-dependent stimulation of exocytosis, and half-maximal effect was observed at 22 microM. The stimulatory effect of InsP6 was dependent on protein kinase C (PKC) activity. Antisense oligonucleotides directed against specific PKC isoforms (alpha, beta II, delta, epsilon, xi) revealed the involvement of PKC-epsilon in InsP6-induced exocytosis. Furthermore, expression of dominant negative PKC-epsilon abolished InsP6-evoked exocytosis, whereas expression of wild-type PKC-epsilon led to a significant stimulation of InsP6-induced exocytosis. These data demonstrate that PKC-epsilon is involved in InsP6-induced exocytosis in pancreatic beta-cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / pharmacology
  • Cyclosporine / pharmacology
  • Exocytosis / drug effects
  • Exocytosis / physiology*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / physiology*
  • Kinetics
  • Mice
  • Models, Biological
  • Okadaic Acid / pharmacology
  • Permethrin / pharmacology
  • Phytic Acid / pharmacology*
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein Kinase C-epsilon
  • Recombinant Proteins / metabolism


  • Recombinant Proteins
  • Okadaic Acid
  • Permethrin
  • Phytic Acid
  • Cyclosporine
  • Prkce protein, mouse
  • Protein Kinase C
  • Protein Kinase C-epsilon
  • Calcium