Rutin alleviates advanced glycosylation end products-induced insulin resistance by inhibiting SOCS3/IRS1 and activating PI3K/AKT signaling pathways in HepG2 cells
Yuling Jiang, Li Wang, Fangyu Fan, Qichen Fang, Huating Li, Mingfu Wang, Yueliang Zhao
Abstract
• Rutin showed the most potent AGEs inhibitory capacity in both food and HepG2 cell models. • Rutin mitigated glucose metabolism disorders induced by AGEs in HepG2 cells. • Rutin alleviated AGEs-induced insulin resistance via SOCS3/IRS1 and PI3K/AKT pathways. • PI3K/AKT pathway played an important role in enhancing insulin sensitivity in response to rutin. The accumulation of advanced glycosylation end products (AGEs) from food in the body disrupts normal physiological insulin activity and causes insulin resistance. This study compared the effects of ten types of polyphenols on AGEs production in both chemical and food models. It also investigated the impact of polyphenols on AGEs-induced insulin resistance in HepG2 cell models. Results showed that luteolin had the strongest inhibitory effect on fluorescent AGEs in the three chemical models. Rutin exhibited the most potent capacity to inhibit AGEs in biscuit models. Moreover, rutin alleviated the glucose metabolism disorders induced by representative AGEs (methylglyoxal-modified bovine serum albumin, MGO-BSA) in HepG2 cells. Mechanistic studies revealed that rutin could inhibit the phosphorylation of insulin receptor substrate 1 (IRS1) and the activity of suppressor of cytokine signaling 3 (SOCS3), while activating the phosphorylation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) to alleviate the MGO-BSA-induced insulin resistance in HepG2 cells.