Persistent activation of Akt or ERK prevents the toxicity induced by saturated and polyunsaturated fatty acids in RINm5F β-cells

The aim of this study was to investigate whether the toxicity of saturated and polyunsaturated fatty acids (PUFA) on RINm5F cells is related to the phosphorylation state of Akt, ERK and PKCδ. The regulation of these kinases was compared in three experimental designs: (a) 4 h-exposure, (b) 4 h-exposure and a subsequent withdrawn of the FA for a 20 h period and (c) 24 h-exposure. Saturated and PUFA were toxic to RINm5F cells even at low concentrations. Also, evidence is provided for a late (i.e. the effect only appeared hours after the treatment) and a persistent regulation (i.e. maintenance of the effect for several hours) of Akt, ERK and PKCδ phosphorylation by the FA. Late activation of PKCδ seems important for palmitate cytotoxicity. Persistent activation of the survival proteins Akt and ERK by stearate, oleate and arachidonate might play an important role to prevent the toxic effect of posterior PKCδ activation. The results shown may explain why a short-period exposure to FA is not enough to induce cytotoxicity in pancreatic β-cells, since survival pathways are activated. Besides, when this activation is persistent, it may overcome a posterior induction of death pathways.