Increased fatty acid desaturation and enhanced expression of stearoyl coenzyme A desaturase protects pancreatic β-cells from lipoapoptosis

Anna K. Busch, Ebru Gurisik, Damien V. Cordery, Michelle Sudlow, Gareth S. Denyer, D. Ross Laybutt, William E. Hughes, Trevor J. Biden

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Abstract

Increased availability of fatty acids causes cell death and dysfunction in β-cell lines, isolated islets, and animal models of diabetes. From the MIN6 β-cell line, we selected two subpools that are resistant to palmitate-induced apoptosis. Protection was not universal because palmitate-resistant cells remained sensitive to cytokine- and streptozotocin-induced apoptosis. Palmitate oxidation and incorporation into cholesterol ester (but not triglycerides) were significantly higher in palmitate-resistant cells than in control cells. Consistent with these findings, transcript profiling revealed increased expression in palmitate-resistant cells of several β-oxidation genes as well as a 2.8-fold upregulation of stearoyl-CoA desaturase 1 (SCD1). Correspondingly, the oleate-to-palmitate ratio of palmitate-resistant cells was double that of palmitate-pretreated control cells. At least some of this additional oleate in palmitate-resistant cells was incorporated into cholesterol ester stored in the form of large cytosolic lipid bodies. However, blocking cholesterol ester formation did not render palmitate-resistant cells sensitive to palmitate-induced apoptosis. On the other hand, an inhibitor of SCD1, 10,12-conjugated linoleic acid, dose dependently overcame the resistance of palmitate-resistant cells to lipoapoptosis. Our results suggest that desaturation per se is more important in protecting β-cells from the cytotoxic effects of palmitate than is the nature of neutral lipid storage pool thus generated.

Original languageEnglish
Pages (from-to)2917-2924
Number of pages8
JournalDiabetes
Volume54
Issue number10
DOIs
Publication statusPublished - 1 Oct 2005
Externally publishedYes

Cite this

Busch, A. K., Gurisik, E., Cordery, D. V., Sudlow, M., Denyer, G. S., Ross Laybutt, D., Hughes, W. E., & Biden, T. J. (2005). Increased fatty acid desaturation and enhanced expression of stearoyl coenzyme A desaturase protects pancreatic β-cells from lipoapoptosis. Diabetes, 54(10), 2917-2924. https://doi.org/10.2337/diabetes.54.10.2917