In this study, we observed that PTP1B has three O-GlcNAc sites: Ser104, Ser201, Ser386; O-GlcNAcylation of PTP1B is increased in insulin resistance; and intervention PTP1B O-GlcNAcylation can recover insulin sensitivity and improve lipid deposition in HepG2 cells. The gene discussed is PTPN1; the disease is Insulin resistance.