Combined with our results that hyperphosphorylated IRS-1 on serine 307 site and reduced IRS-1 protein were detected in TNF-α-induced hepatic insulin resistance, we speculated that PP4 promoted IRS-1 phosphorylation through JNK activation, thus resulting in IRS-1 degradation via proteasome degradation system. This evidence concerns the gene MAPK8 and Insulin resistance.