PKCdelta-dependent phosphorylation of 14 – 3-3zeta delays the nuclear export of FOXO1 in beta-cells

Background and aim: Fatty acid-induced beta-cell death accounts for insulin deficiency during the onset of obesity-linked diabetes. Previous observations suggest that inhibition of PKCdelta impairs nuclear accumulation of FOXO1 and protects against palmitate-induced apoptosis. The present study aims at examining the mechanism of PKCdelta-dependent nucleo-cytoplasmic shuttling of FOXO1 and its relevance for fatty acid-associated beta-cell failure. Methods: Expression of PKCdelta was genetically modified in mice and INS-1E cells. Apoptosis was assessed by TUNEL staining. Subcellular localisation of proteins was vi…