GSK3B and Insulin resistance: On the other hand, DOX has also been demonstrated to induce oxidative stress in skeletal muscle without altering LDH (van Norren et al., 2009) but to cause insulin resistance in muscle by downregulating IRS-1, glucose transporter type 4 (GLUT4), AMPK and glycogen synthase kinase 3 beta (GSK3β) (Hayward et al., 2013).