The association of phosphoinositide 3-kinase enhancer A with hepatic insulin receptor enhances its kinase activity
The association of phosphoinositide 3-kinase enhancer A with hepatic insulin receptor enhances its kinase activity
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DOI：
10.1038/embor.2011.108
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发表时间：
2011-08-01
期刊：
影响因子：
7.7
通讯作者：
Ye, Keqiang
中科院分区：
文献类型：
--
作者：
Chan, Chi Bun;Liu, Xia;Ye, Keqiang
肝脏胰岛素受体酪氨酸激酶（IRTK）功能障碍可导致2型糖尿病的发生。然而，肝脏中调节IRTK活性的分子机制仍然知之甚少。在这里，我们发现磷酸肌肽3-激酶增强子A （PIKE-A）是一种新的胰岛素依赖性肝脏IRTK增强子。肝脏特异性pike敲除（LPKO）小鼠表现为葡萄糖不耐受，肝脏胰岛素敏感性受损。具体来说，胰岛素引起的磷酸肌肽3-激酶/Akt信号在LPKO小鼠肝脏中减弱，导致胰岛素抑制的糖异生失败和高血糖。因此，肝脏PIKE-A在介导胰岛素信号转导和调节肝脏葡萄糖稳态中起关键作用。
Dysfunction of hepatic insulin receptor tyrosine kinase (IRTK) causes the development of type 2 diabetes. However, the molecular mechanism regulating IRTK activity in the liver remains poorly understood. Here, we show that phosphoinositide 3-kinase enhancer A (PIKE-A) is a new insulin-dependent enhancer of hepatic IRTK. Liver-specific Pike-knockout (LPKO) mice display glucose intolerance with impaired hepatic insulin sensitivity. Specifically, insulin-provoked phosphoinositide 3-kinase/Akt signalling is diminished in the liver of LPKO mice, leading to the failure of insulin-suppressed gluconeogenesis and hyperglycaemia. Thus, hepatic PIKE-A has a key role in mediating insulin signal transduction and regulating glucose homeostasis in the liver.