Rutin inhibits hepatic gluconeogenesis and increases glycogen synthesis through the IRS/PI3K/akt signaling pathway in insulin resistant hepatocytes

Rutin, a dietary flavonoid, can relieve insulin resistance to improve hyperglycemia, while the precise mechanism remains unclear. In this study, we found that rutin bound well to the insulin receptor, alleviated glucosamine-induced insulin resistance in HepG2 cells and observably increased glucose consumption and glucose uptake <i>in vitro</i>. Furthermore, rutin increased the levels of IRS-1, IRS-2, PI3K, p-AKT, p-GSK3β and p-FOXO1 and decreased the expression of p-IRS-1, p-GS, PEPCK and G6Pase, indicating that rutin could promote glycogen synthesis and inhibit gluconeogenesis via the IRS/PI3K/Akt signaling pathway. Overall, the findings confirmed that rutin potentially mitigates glucosamine-induced insulin resistance in hepatocytes via activation of IRS/PI3K/Akt pathways.