PEG-Loxe, Lira, and Loxe activated the hepatic insulin signaling pathway in T2DM mice, as evidenced by pointedly elevated p-IRS-1, p-PI3K, p-AKT, and GLUT4 levels and considerably diminished p-GSK-3β expression (Figure 5A). The gene discussed is IRS1; the disease is type 2 diabetes mellitus.