Drak2 Overexpression Results in Increased β-Cell Apoptosis After Free Fatty Acid Stimulation
Drak2 Overexpression Results in Increased β-Cell Apoptosis After Free Fatty Acid Stimulation
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DOI：
10.1002/jcb.21910
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发表时间：
2008-11-01
影响因子：
4
通讯作者：
Wui, Jiangping
中科院分区：
文献类型：
--
作者：
Mao, Jianning;Luo, Hongyu;Wui, Jiangping
Drak2 是死亡相关蛋白家族中的一种丝氨酸苏氨酸激酶。在这项研究中，我们研究了它在游离脂肪酸（FFA）诱导的胰岛细胞凋亡中的作用。 FFA 刺激后，Drak2 mRNA 和蛋白质在胰岛 P 细胞中快速诱导。这种 Drak2 上调伴随着 P 细胞凋亡的增加，而使用 siRNA 敲低 Drak2 可以抑制 P 细胞凋亡。相反，转基因（Tg）Drak2过度表达导致FFA引发的P细胞凋亡加剧。在 FFA 攻击后，Drak2 在胰岛中的过度表达会损害抗凋亡因子（例如 Bcl-2、Bcl-xL 和 Flip）的增加。进一步的体内实验表明，Drak2 Tg 小鼠在饮食诱导的肥胖模型中表现出葡萄糖耐量受损。我们的数据表明，在脂质过多的情况下，Drak2 不利于胰岛存活。 J.细胞。生物化学。 105: 1073-1080, 2008。(C) 2008 Wiley-Liss, Inc.
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.