Reduced levels of SCD1 accentuate palmitate-induced stress in insulin-producing β-cells

Insulin-secreting MIN6 cells with reduced levels of SCD1 were established by siRNA mediated knockdown. When fatty acid oxidation was measured, no difference between cells with reduced levels of SCD1 and mock-transfected cells were found. Also, reducing levels of SCD1 did not affect insulin secretion in response to glucose. To investigate how SCD1 knockdown affected cellular mechanisms, differentially regulated proteins were identified by a proteomic approach. Cells with reduced levels of SCD1 had higher levels of ER chaperones and components of the proteasome. The higher amounts did not protect the β-cell from palmitate-induced ER stress and apoptosis. Instead, rise in levels of p-eIF2α and CHOP after palmitate exposure was 2-fold higher in cells with reduced levels of SCD1 compared to mock-transfected cells. Accordingly, apoptosis rose to higher levels after exposure to palmitate in cells with reduced levels of SCD1 compared to mock-transfected cells.In conclusion, reduced levels of SCD1 augment palmitate-induced ER stress and apoptosis in the β-cell, which is an important caveat when considering targeting this enzyme as a treatment of the metabolic syndrome.Stearoyl-CoA desaturases (SCD:s) are a family of endoplasmic reticulum (ER) resident enzymes introducing a Δ9 double-bond in saturated fatty acids, thereby generating their monounsaturated counterparts [1]. In mice, four isoforms of SCD have been characterized, which all catalyze the same reaction but have somewhat different substrate specificities [1]. The physiological role of having multiple isoforms is not fully understood, but the different expression patterns and inducibility indicate exclusive roles for the different isoforms [2]. In humans, only one functional ortholog to mouse SCD has been found [3]. In addition, humans express another SCD isoform, termed hSCD5, which is unique to primates [4]. Much focus has been directed towards the SCD1 isoform, which is ubiquitously expressed in mouse, and the majo