Involvement of protein kinase C-ε in inositol hexakisphosphate-induced exocytosis in mouse pancreatic β-cells

Inositolhexakisphosphate (InsP(6)) plays a pivotal role in the pancreatic beta-cell stimulus-secretion coupling. We have used capacitance measurements to study the effects of InsP(6) 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 InsP(6) produced a dose-dependent stimulation of exocytosis, and half-maximal effect was observed at 22 muM. The stimulatory effect of InsP6 was dependent on protein kinase C (PKC) activity. Antisense oligonucleotides directed against specific PKC isoforms (alpha, betaII, delta, epsilon, xi) revealed the involvement of PKC-epsilon in InsP(6)-induced exocytosis. Furthermore, expression of dominant negative PKC-epsilon abolished InsP(6)-evoked exocytosis, whereas expression of wild-type PKC-epsilon led to a significant stimulation of InsP(6)-induced exocytosis. These data demonstrate that PKC-epsilon is involved in InsP(6)-induced exocytosis in pancreatic beta-cells.