MAPK8 and Insulin resistance: Insulin resistance and hyperglycemia stimulate IGF-1 signaling, and IGF-1 then activates oncogenic signaling pathways such as PI3K/Akt/mTOR, JNK/MAPK, Wnt, and Ras/MEK/ERK, which promote cell proliferation and angiogenesis and inhibit apoptosis, eventually fostering the development of HCC [33].