Faculty of Life Sciences, The University of Manchester, 2nd Floor Core Technology Facility, 46 Grafton Street, Manchester, M13 9NT, UK.
Pflugers Arch. 2011 Nov;462(5):723-32. doi: 10.1007/s00424-011-1008-4. Epub 2011 Aug 17.
The phosphoinositide phospholipid PtdIns5P has previously been implicated in insulin-stimulated translocation of the glucose transporter GLUT4 into the plasma membrane of adipocytes, but its potential role in glucose transport in muscle has not been explored. The involvement of PtdIns5P in insulin-stimulated glucose uptake was therefore investigated in myotubes of the skeletal muscle cell line L6. Stimulation with insulin produced a transient increase in PtdIns5P, which was abolished by the over-expression of the highly active PtdIns5P 4-kinase PIP4Kα. PIP4Kα over-expression also abolished both the enhanced glucose uptake and the robust peak of PtdIns(3,4,5)P (3) production stimulated by insulin in myotubes. Delivery of exogenous PtdIns5P into unstimulated myotubes increased Akt phosphorylation, promoted GLUT4 relocalisation from internal membrane to plasma membrane fractions and its association with plasma membrane lawns and also stimulated glucose uptake in a tyrosine kinase and phosphoinositide 3-kinase (PI 3-kinase)-dependent fashion. Our results are consistent with a role for insulin-stimulated PtdIns5P production in regulating glucose transport by promoting PI 3-kinase signalling.
磷酸肌醇磷脂 PtdIns5P 先前被认为参与了胰岛素刺激脂肪细胞中葡萄糖转运蛋白 GLUT4 向质膜的易位，但它在肌肉中葡萄糖转运的潜在作用尚未被探索。因此，我们研究了骨骼肌细胞系 L6 的肌管中 PtdIns5P 在胰岛素刺激的葡萄糖摄取中的作用。胰岛素刺激产生了 PtdIns5P 的短暂增加，而过表达高度活跃的 PtdIns5P 4-激酶 PIP4Kα 则消除了这种增加。PIP4Kα 的过表达也消除了胰岛素刺激肌管中增强的葡萄糖摄取和 PtdIns(3,4,5)P3 的强烈峰值。将外源性 PtdIns5P 递送到未受刺激的肌管中会增加 Akt 的磷酸化，促进 GLUT4 从内膜重新定位到质膜部分，并与质膜草坪结合，还会以酪氨酸激酶和磷酸肌醇 3-激酶 (PI 3-kinase) 依赖的方式刺激葡萄糖摄取。我们的结果与胰岛素刺激的 PtdIns5P 产生在通过促进 PI 3-kinase 信号转导来调节葡萄糖转运中的作用一致。
