Drak2 Overexpression Results in Increased β-Cell Apoptosis After Free Fatty Acid Stimulation

Drak2 is a serine threonine kinase in the death-associated protein family. In this study, we investigated its role in free Fatty acid (FFA)-induced islet apoptosis. Drak2 mRNA and protein were rapidly induced in islet P-cells after FFA stimulation. Such Drak2 upregulation was accompanied by increased P-cell apoptosis, which was inhibited by Drak2 knockdown using siRNA. Conversely, transgenic (Tg) Drak2 overexpression led to aggravated P-cell apoptosis triggered by FFA. Drak2 overexpression in islets compromised the increase of antiapoptotic factors, such as Bcl-2, Bcl-xL and Flip, upon FFA assault. Further in vivo experiments demonstrated that Drak2 Tg mice presented compromised glucose tolerance in a diet-induced obesity model. Our data show that Drak2 is detrimental to islet survival in the presence of excessive lipid. J. Cell. Biochem. 105: 1073-1080, 2008. (C) 2008 Wiley-Liss, Inc.