Insulin Receptor Signals Regulating GLUT4 Translocation and Actin Dynamics

Abstract

In skeletal muscle and adipose tissue, insulin-stimulated glucose uptake is dependent upon translocation of the insulin-responsive glucose transporter GLUT4 from intracellular storage compartments to the plasma membrane. This insulin-induced redistribution of GLUT4 protein is achieved through a series of highly organized membrane trafficking events, orchestrated by insulin receptor signals. Recently, several key molecules linking insulin receptor signals and membrane trafficking have been identified, and emerging evidence supports the importance of subcellular compartmentalization of signaling components at the right time and in the right place. In addition, the translocation of GLUT4 in adipocytes requires insulin stimulation of dynamic actin remodeling at the inner surface of the plasma membrane (cortical actin) and in the perinuclear region. This results from at least two independent insulin receptor signals, one leading to the activation of phosphatidylinositol (PI) 3-kinase and the other to the activation of the Rho family small GTP-binding protein TC10. Thus, both spatial and temporal regulations of actin dynamics, both beneath the plasma membrane and around endomembranes, by insulin receptor signals are also involved in the process of GLUT4 translocation.