IRS1 and obesity due to melanocortin 4 receptor deficiency: Firstly, DNA methylation regulates different insulin signaling genes, such as insulin (INS), insulin receptor substrate 1 (IRS1), Insulin-like growth factor-1/2 (IGF-1/2), Insulin-like growth factor-binding protein 1/2 (IGFBP-1/2), phosphatidylinositol 3-kinase regulatory subunit (PIK3R1), and Glucagon-like peptide-1 receptor (GLP-1R).203–206 The methylation status of these genes was found to be altered in obesity and IR.