Oleanolic acid attenuates insulin resistance via NF-kappaB to regulate IRS1-GLUT4 pathway in HepG2 c

• 作 者: ZongyuHan;XuguangHu;WeijianBei;JiaoGuo;
• 出 处: 世界中医药学会联合会中药药理专业委员会第七届学术会议、全国中药药理联合会第二届学术年会暨第20届中日健康学术研讨会
• 发表日期: 2014年期

Background:Insulin resistance (IR) is a risk factor for many clinical diseases,including type Ⅱ diabetes,hypertension,atherosclerosis.It plays an important role in the research of metabolic syndrome (MS) in recent years.Fu Fang Zhen Zhu Tiao Zhi formula (FTZ),a Chinese medicinal decoction,has been used to relieve hyperlipidemia,atherosclerosis and other symptoms associated with metabolic disorders in the clinic.Our study has found that FTZ also had the role of preventing insulin resistance and the mechanism related to IRSl pathway.Glossy privet fruit (GPF) in this formula and oleanolic acid (OA) which is the mainly effective active ingredient of GPF have significant effect to insulin resistance and anti-inflammatory.Nevertheless,the effect and mechanisms of GPF and OA on insulin resistance remain unclear.Methods:To compare and evaluate the effect of FTZ,GPF and OA on insulin resistance,HepG2 cells were induced with free fatty acid (FFA) as a model of insulin resistance and treated with FTZ,GPF and OA.The level of glucose content was measured.Then to study the mechanism of OA on insulin resistance HepG2 cells which were induced with FFA.The level of glucose content,the content of tumor necrosis factor-a (TNF-α) and interleukin-6 (IL-6),nuclear factor kappa B (NF-κB),insulin receptor substrate l(IRSl) and glucosetransporter 4 (GLUT4) protein expression effected by OA at three dosages were measured.After using PDTC (one of the NF-κB inhibitors),IRS1 protein expression by treating with OA was measured.Results:Our results revealed that FTZ,GPF and OA attenuated glucose content.OA was the best.OA attenuated glucose content and up-regulated the expression of IRSl and GLUT4 protein.Moreover,OA reduced the content of TNF-α and IL-6 as well as the expression of NF-TCB protein in insulin-resistant HepG2 cell in vitro.After blocking NF-κB,IRS1 protein expression retumed to normal level as Control group.And had no obvious change even added OA.Conclusion:OA attenuated insulin resistance symptoms by decreasing the culture medium levels of inflammatory cytokines.The underlying mechanism of OA relieved insulin resistance was regulated NF-κB to affect IRSI-GLUT4 pathway.