AS160与TBC1D1:胰岛素和运动/骨骼肌收缩诱导葡萄糖转运的汇聚点

AS160 and TBC1D1:Convergence of Exercise-and Insulin-Stimulated Glucose Transport in Skeletal Muscle

运动和胰岛素是诱导骨骼肌葡萄糖转运的两种重要生理因素,两者均能通过不同的信号转导通路诱导GLUT4从细胞内转位到细胞膜表面,从而调控骨骼肌的葡萄糖转运。研究表明,TBC1家族结构域家族成员蛋白激酶B蛋白底物160KDa(AS160/TBC1D4)和TBC1D1这两种同源蛋白均可在运动或胰岛素诱导下发生磷酸化,两者可能是运动和胰岛素调控骨骼肌葡萄糖转运信号通路的关键汇聚点。综述AS160与TBC1D1在胰岛素诱导骨骼肌葡萄糖转运中的不同作用以及运动/骨骼肌收缩对其的影响及其机制,以期深入了解运动如何改善胰岛素敏感性、为更科学的运动处方及其他干预措施的研发提供有价值的理论支持。

Skeletal muscle accounts for the largest amount of insulin-stimulated blood glucose clearance. Defects in skeletal muscle insulin signaling which are responsible for causes of insulin resistance. The major physiological stimuli that activate skeletal muscle glucose transport are insulin and exercise, and insulin and exercise regulate skeletal muscle glucose trans-port by increasing the number of cell surface GLUT4 glucose transporters. Multiple lines of evidence suggest that the mechanism of insulin and exercise on glucose transport are distinct. Two members of the TBC1 domain family of proteins, Akt substrate of 160 kDa （also known as AS160 or TBC1D4） and TBC1D1, become phosphorylated with exercise-or insu-lin-stimulation, and they have been proposed as potential sites for the convergence of insulin and exercise signaling to stimulate glucose transport in skeletal muscle. This review will provide a summary of recent research and our speculative interpretation regarding the relationship of AS160 and TBC1D1 with skeletal muscle glucose transport and the effect of ex-ercise/contraction on AS160 and TBC1D1, that will be to better understand how exercise improve insulin sensitivity and provide valuable insights that can be used for development alternative interventions.