Drak2 overexpression results in increased β-cell apoptosis after free fatty acid stimulation

✍ Scribed by Jianning Mao; Hongyu Luo; Jiangping Wu

• Book ID: 102304710
• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 233 KB
• Volume: 105
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.21910

✦ Synopsis

Abstract

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 β‐cells after FFA stimulation. Such Drak2 upregulation was accompanied by increased β‐cell apoptosis, which was inhibited by Drak2 knockdown using siRNA. Conversely, transgenic (Tg) Drak2 overexpression led to aggravated β‐cell apoptosis triggered by FFA. Drak2 overexpression in islets compromised the increase of anti‐apoptotic 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. © 2008 Wiley‐Liss, Inc.