Reciprocally, changes in O-GlcNAc levels of specific proteins and sites are responsible for hepatic insulin resistance, glucose toxicity, insulin-induced de novo lipogenesis, necroptosis, and tissue fibrosis, contributing to the development of metabolic diseases (Zhang et al., 2014, 2019, 2021a; Banerjee et al., 2016). The gene discussed is INS; the disease is metabolic disease.