IRS2 and Insulin resistance: Insulin/IGF-1 signal was impaired in the chronic stress conditions, which might cause insulin resistance, hyperglycemia, a prothrombotic state, and diabetic skeletal muscle disorder.5 We also observed that stress resulted in decreases in the levels of p-PI3K, p-Akt, and p-mTOR proteins and GLUT-4 gene located downstream of the IGF-1/IRS-2 signaling pathway, and that CTSS−/− reversed these molecule changes after stress (Fig. 4a–c, Suppl.