MAPK8 and Insulin resistance: To further demonstrate the involvement of ER stress in PDE5A-induced insulin resistance, STF-083010 (STF), a novel small-molecule inhibitor of IRE1 [20], was used to inhibit IRE1-mediated branch of the unfounded protein response (UPR), which has been recognized as a critical mediator of ER stress-induced insulin resistance in myotubes by activating JNK/IRS-1 pathway [21].