Differential regulation of the ER stress response by long-chain fatty acids in the pancreatic β-cell

Recent evidence indicates that treatment of pancreatic β-cells with long chain fatty acids can lead to the development of an ER (endoplasmic reticulum) stress response. This is manifest as the activation of some components of the PERK [RNA-dependent protein kinase-like ER eIF2α (eukaryotic initiation factor 2α) kinase]-dependent arm of ER stress and is seen most dramatically when cells are treated with long-chain saturated fatty acids (e.g. palmitate). By contrast, the equivalent mono-unsaturates (e.g. palmitoleate) are much less effective and they can even attenuate the ER stress response to palmitate. This may be due to the regulation of eIF2α phosphorylation in cells exposed to mono-unsaturates. The present review discusses the differential effects of saturated and mono-unsaturated fatty acids on ER stress in β-cells and considers the extent to which regulation of this pathway may be involved in mediating their effects on viability.