Involvement of protein kinase C-epsilon in inositol hexakisphosphate-induced exocytosis in mouse pancreatic beta-cells.
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.
Høy
Marianne
M
Laboratory of Islet Cell Physiology, Novo Nordisk A/S, Novo Alle, DK-2880 Bagsvaerd, Denmark.
Berggren
Per-Olof
PO
Gromada
Jesper
J
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D019319:Okadaic Acid / Q000494:pharmacology; D026023:Permethrin / Q000494:pharmacology; D010833:Phytic Acid / Q000494:pharmacology*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051744:Protein Kinase C-epsilon; D011994:Recombinant Proteins / Q000378:metabolism
D011994:Recombinant Proteins; D019319:Okadaic Acid; D026023:Permethrin; D010833:Phytic Acid; D016572:Cyclosporine; C497256:Prkce protein, mouse; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D002118:Calcium