Exercise-associated differences in an array of proteins involved in signal transduction and glucose transport

Vastus lateralismuscle biopsies were obtained from endurance-trained (running ~50km/wk) and untrained (no regular physical exercise) men, and theexpression of an array of insulin-signaling intermediates wasdetermined. Expression of insulin receptor and insulin receptorsubstrate-1 and -2 was decreased 44% (P < 0.05), 57%(P < 0.001), and 77% (P < 0.001),respectively, in trained vs. untrained muscle. The downstream signalingtarget, Akt kinase, was not altered in trained subjects. Components ofthe mitogenic signaling cascade were also assessed. Extracellularsignal-regulated kinase 1/2 mitogen-activated protein kinase expressionwas 190% greater (P < 0.05), whereas p38 mitogen-activatedprotein kinase expression was 32% lower (P < 0.05), intrained vs. untrained muscle. GLUT-4 protein expression was twofoldhigher (P < 0.05), and the GLUT-4 vesicle-associatedprotein, the insulin-regulated aminopeptidase, was increased 4.7-fold(P < 0.05) in trained muscle. In conclusion, the expressionof proteins involved in signal transduction is altered in skeletalmuscle from well-trained athletes. Downregulation of early componentsof the insulin-signaling cascade may occur in response to increasedinsulin sensitivity associated with endurance training.