Insulin signaling and physical activity in skeletal muscle

Abstract

Skeletal muscle is vital for regulating blood glucose, increasing the incorporation of glucose both through insulin and through physical activity. The increase in insulin causes the activation of its receptor, triggering an important signaling cascade in which modulators such as IRS, PI3K, Akt, AS160 (TBC1D4), Rac-1, actin remodeling, etc. intervene. Regarding the activation triggered by physical exercise, the signaling pathways elucidated so far have proven to be essential in this process. Among the most studied pathways we find: the activation of 5ʹ AMP-activated protein kinase (AMPK), the increase in calcium and the activation of calcium sensor proteins (CaMKK, CaMKII and nPKC), which in turn modify its state of phosphorylation after exercise, and a series of stretch-sensitive proteins that allow the activation of Rac1, PAK, actin remodeling, etc. Thus, both stimuli (insulin and physical activity) increase glucose transport thanks to the activation of two essential processes: the trafficking of GLUT4 transport vesicles and their fusion with the plasma membrane. Vesicle trafficking requires Rabs proteins (Rab8 and Rab13), while membrane fusion requires the participation of proteins capable of fusing the vesicle and plasma membranes, and SNAREs (Syntaxin4, SNAP23 and VAMP2). Finally, these events allow the increase of GLUT4 on the cell surface, which enables glucose uptake and a decrease in blood glucose.