Reduced level of SCD1 sensitizes the β-cell to palmitate-induced stress
2010 (English)In: PLoS ONE, ISSN 1932-6203Article in journal (Refereed) Submitted
Background: Stearoyl-CoA desaturase 1 (SCD1) is an ER resident enzyme introducing a double-bond in saturated fatty acids. Global knock out of SCD1 in the mouse increases fatty acid oxidation and insulin sensitivity which makes the animal resistant to diet-induced obesity and inhibition of SCD1 has therefore been proposed as a potential therapy of the metabolic syndrome. Much of the work has focused on insulin target tissue and very little is known about how reduced levels of SCD1 would affect the insulin-producing β-cell, however. The aim of the present study was therefore to investigate how reduced levels of SCD1 affect the β-cell. Methodology/Principal Findings: Insulin-secreting MIN6 cells with reduced levels of SCD1 were established by siRNA mediated knock-down. 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 knock-down 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, however. Rather, 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. In agreement, apoptosis rose to higher levels after exposure to palmitate in cells with reduced levels of SCD1 compared to mock-transfected cells. Conclusions/Significance: In conclusion, SCD1 sensitizes the β-cell to palmitate-induced ER stress and apoptosis, which is an important caveat when considering targeting this enzyme as a treatment of the metabolic syndrome.
Place, publisher, year, edition, pages
SCD1, ER stress, palmitate, AMPK, proteomics, apoptosis
Cell and Molecular Biology
Research subject Medical Cell Biology
IdentifiersURN: urn:nbn:se:uu:diva-129573OAI: oai:DiVA.org:uu-129573DiVA: diva2:344342