Expression, phosphorylation and function of the Rab-GTPase activating protein TBC1D1 in pancreatic beta-cells
Expression, phosphorylation and function of the Rab-GTPase activating protein TBC1D1 in pancreatic beta-cells
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Rab-GTPase 激活蛋白 TBC1D1 在胰腺 β 细胞中的表达、磷酸化和功能
DOI：
10.1016/j.febslet.2013.10.050
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Bouzakri K.
中科院分区：
文献类型：
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作者：
Rutti S;Arous C;Nica AC;Kanzaki M;Halban PA;Bouzakri K.
Rab-GT3激活蛋白TBC 1D 1是AS 160/TBC 1D 4的一个同源蛋白。AS 160/TBC 1D 4是Akt的下游效应子，已被证明在β细胞功能和存活中发挥核心作用。这两种蛋白质在肌肉细胞中的胰岛素信号传导中具有重叠的功能。然而，TBC 1D 1在β细胞中的表达和潜在作用仍然未知。因此，本研究的目的是研究TBC 1D 1是否在β细胞中表达，以及它是否像AS 160/TBC 1D 4一样在β细胞功能和存活中发挥作用。使用人类和大鼠β细胞，这项研究首次表明TBC 1D 1在这些细胞中响应葡萄糖而表达和磷酸化。β细胞中TBC 1D 1的敲低导致基础和葡萄糖刺激的胰岛素释放增加，增殖减少，但凋亡没有变化。
The Rab-GTPase activating protein TBC1D1 is a paralog of AS160/TBC1D4. AS160/TBC1D4, a downstream effector of Akt, has been shown to play a central role in beta-cell function and survival. The two proteins have overlapping function in insulin signalling in muscle cells. However, the expression and the potential role of TBC1D1 in beta-cells remain unknown. Therefore, the aim of this study is to investigate whether TBC1D1 is expressed in beta-cells and whether it plays, as AS160/TBC1D4, a role in beta-cell function and survival. Using human and rat beta-cells, this study shows for the first time that TBC1D1 is expressed and phosphorylated in response to glucose in these cells. Knockdown of TBC1D1 in beta-cells resulted in increased basal and glucose-stimulated insulin release, decreased proliferation but no change in apoptosis.