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Reduced levels of SCD1 accentuate palmitate-induced stress in insulin-producing beta-cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
2010 (English)In: Lipids in Health and Disease, ISSN 1476-511X, E-ISSN 1476-511X, Vol. 9, 108- p.Article in journal (Refereed) Published
Abstract [en]

Background: Stearoyl-CoA desaturase 1 (SCD1) is an ER resident enzyme introducing a double-bond in saturated fatty acids. Global knockout of SCD1 in mouse increases fatty acid oxidation and insulin sensitivity which makes the animal resistant to diet-induced obesity. 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 beta-cell, however. The aim of the present study was therefore to investigate how reduced levels of SCD1 affect the beta-cell. Results: 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 beta-cell from palmitate-induced ER stress and apoptosis. Instead, rise in levels of p-eIF2 alpha 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. Conclusions: In conclusion, reduced levels of SCD1 augment palmitate-induced ER stress and apoptosis in the beta-cell, which is an important caveat when considering targeting this enzyme as a treatment of the metabolic syndrome.

Place, publisher, year, edition, pages
2010. Vol. 9, 108- p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-133594DOI: 10.1186/1476-511X-9-108ISI: 000283174500001OAI: oai:DiVA.org:uu-133594DiVA: diva2:370175
Available from: 2010-11-15 Created: 2010-11-11 Last updated: 2017-12-12Bibliographically approved

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