Metabolic Research Laboratories, Wellcome-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, U.K.
Department for Health, Centre for Nutrition, Exercise, and Metabolism, University of Bath, Bath, Somerset BA2 7AY, U.K.
Biochem J. 2022 Feb 11;479(3):445-462. doi: 10.1042/BCJ20210073.
Insulin rapidly stimulates GLUT4 translocation and glucose transport in fat and muscle cells. Signals from the occupied insulin receptor are translated into downstream signalling changes in serine/threonine kinases within timescales of seconds, and this is followed by delivery and accumulation of the glucose transporter GLUT4 at the plasma membrane. Kinetic studies have led to realisation that there are distinct phases of this stimulation by insulin. There is a rapid initial burst of GLUT4 delivered to the cell surface from a subcellular reservoir compartment and this is followed by a steady-state level of continuing stimulation in which GLUT4 recycles through a large itinerary of subcellular locations. Here, we provide an overview of the phases of insulin stimulation of GLUT4 translocation and the molecules that are currently considered to activate these trafficking steps. Furthermore, we suggest how use of new experimental approaches together with phospho-proteomic data may help to further identify mechanisms for activation of these trafficking processes.
胰岛素能迅速刺激脂肪细胞和肌肉细胞中的 GLUT4 易位和葡萄糖转运。在几秒钟的时间内，被占据的胰岛素受体发出的信号会转化为丝氨酸/苏氨酸激酶的下游信号变化，随后葡萄糖转运体 GLUT4 被递送到质膜并在该处聚集。动力学研究表明，胰岛素的刺激存在明显的阶段。从亚细胞储库隔间迅速初始爆发 GLUT4 递送到细胞表面，然后是持续刺激的稳定状态，其中 GLUT4 通过大量亚细胞位置的循环进行回收。在这里，我们概述了胰岛素刺激 GLUT4 易位的阶段以及目前被认为能激活这些运输步骤的分子。此外，我们还提出了如何使用新的实验方法和磷酸化蛋白质组学数据来帮助进一步确定激活这些运输过程的机制。
