Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
Exp Cell Res. 2018 May 1;366(1):49-54. doi: 10.1016/j.yexcr.2018.03.011. Epub 2018 Mar 11.
GLUT4 is unique among specialized glucose transporters in being exclusively expressed in muscle and adipocytes. In the absence of insulin the distribution of GLUT4 is preferentially intracellular and insulin stimulation results in the movement of GLUT4 containing vesicles to the plasma membrane. This process is responsible for the insulin stimulation of glucose uptake in muscle and fat. While signalling pathways triggering the translocation of GLUT4 are well understood, the mechanisms regulating the intracellular retention of GLUT4 are less well understood. Here we report a role for β-catenin in this process. In 3T3-L1 adipocytes in which β-catenin is depleted, the levels of GLUT4 at and near the plasma membrane rise in unstimulated cells while the subsequent increase in GLUT4 at the plasma membrane upon insulin stimulation is reduced. Small molecule approaches to acutely activate or inhibit β-catenin give results that support the results obtained with siRNA and these changes are accompanied by matching changes in glucose transport into these cells. Together these results indicate that β-catenin is a previously unrecognized regulator of the mechanisms that control the insulin sensitive pool of GLUT4 transporters inside these adipocyte cells.
GLUT4 在专门的葡萄糖转运蛋白中是独一无二的，仅在肌肉和脂肪细胞中表达。在没有胰岛素的情况下，GLUT4 的分布优先在细胞内，而胰岛素刺激会导致含有 GLUT4 的囊泡向质膜移动。这个过程负责肌肉和脂肪中胰岛素刺激的葡萄糖摄取。虽然触发 GLUT4 易位的信号通路已被很好地理解，但调节 GLUT4 细胞内保留的机制了解较少。在这里，我们报告了β-连环蛋白在这个过程中的作用。在β-连环蛋白耗尽的 3T3-L1 脂肪细胞中，在未刺激的细胞中，靠近质膜的 GLUT4 水平升高，而胰岛素刺激后质膜上 GLUT4 的后续增加减少。急性激活或抑制β-连环蛋白的小分子方法的结果支持 siRNA 获得的结果，并且这些变化伴随着这些细胞中葡萄糖转运的匹配变化。这些结果表明，β-连环蛋白是控制这些脂肪细胞中胰岛素敏感的 GLUT4 转运蛋白池的机制的先前未被认识到的调节剂。
