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

  • J Asian Nat Prod Res. 2025 Nov 16:1-15. doi: 10.1080/10286020.2025.2577900.
Qiu-Hong Li  1 ,  Ming-Xing Lu  1 ,  Yu-Han Feng  1 ,  Mao Zhao  1 ,  Ting-Dan Mo  1 ,  Wen-Wen Jiang  1 ,  Xia Zhang  1 ,  Lu Wang  2
Affiliations
  • 1. School of Pharmaceutical Sciences, Guizhou University, Guiyang 550025, China.
  • 2. Engineering Research Center of the Utilization for Characteristic Bio-Pharmaceutical Resources in Southwest, Ministry of Education, Guizhou University, Guiyang 550025, China.
PMID: 41243335 DOI: 10.1080/10286020.2025.2577900
Abstract

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 in vitro. 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.

Keywords
IRS/PI3K/Akt signaling pathway; Rutin; hepatocytes; insulin resistance.