Department of Newborn Infants, Nanjing Children's Hospital of Nanjing Medical University, Nanjing 210008, PR China.
Mol Med Rep. 2011 May-Jun;4(3):519-23. doi: 10.3892/mmr.2011.443. Epub 2011 Feb 22.
The aim of this study was to investigate whether the early endosome antigen 1 (EEA1) and/or PI3K pathway is involved in the molecular mechanisms underlying the effects of the six-transmembrane protein of prostate 4 (STEAP4; also called STAMP2 and TIARP) on the insulin sensitivity of human adipocytes. Our data demonstrated that siRNA-mediated STEAP4 deficiency significantly decreased insulin-stimulated glucose transport in mature human adipocytes by decreasing GLUT4 translocation to the plasma membrane through attenuated Akt phosphorylation. We further found that EEA1 may not be involved in the mechanisms underlying the effects of STEAP4 on insulin-stimulated glucose uptake and GLUT4 translocation, as indicated by the results that i) STEAP4 does not alter the effects of EEA1 on insulin-stimulated glucose uptake and GLUT4 translocation; ii) STEAP4 does not modify the expression of EEA1 protein; and iii) STEAP4 does not interact with EEA1 according to FRET analysis. In conclusion, this study revealed that the knockdown of STEAP4 inhibits insulin-stimulated glucose transport and GLUT4 translocation via the attenuated phosphorylation of Akt, independent of the effects of EEA1.
本研究旨在探讨早期内体抗原 1（EEA1）和/或 PI3K 通路是否参与六跨膜蛋白前列腺 4（STEAP4；也称为 STAMP2 和 TIARP）对人脂肪细胞胰岛素敏感性的影响的分子机制。我们的数据表明，siRNA 介导的 STEAP4 缺陷通过减弱 Akt 磷酸化使 GLUT4 向质膜易位减少，从而显著降低成熟人脂肪细胞中胰岛素刺激的葡萄糖转运。我们进一步发现，EEA1 可能不参与 STEAP4 对胰岛素刺激的葡萄糖摄取和 GLUT4 易位的影响机制，这表明：i）STEAP4 不改变 EEA1 对胰岛素刺激的葡萄糖摄取和 GLUT4 易位的影响；ii）STEAP4 不改变 EEA1 蛋白的表达；iii）根据 FRET 分析，STEAP4 不与 EEA1 相互作用。总之，本研究揭示了 STEAP4 的敲低通过减弱 Akt 的磷酸化抑制胰岛素刺激的葡萄糖转运和 GLUT4 易位，与 EEA1 的作用无关。
