Study On The Mechanism Of Aucubin On Improving Insulin Resistance

Insulin resistance(IR)can reduce the efficiency of glucose uptake and utilization by insulin target tissues such as fat,liver and skeletal muscle,which can easily lead to the occurrence of type 2 diabetes(T2DM).Therefore,improving IR can help T2 DM Prevention.Studies have found that some iridoid compounds can improve IR.Aucubin(AU),as one of the iridoid glycosides,exists in traditional Chinese medicines such as Eucommia and Rehmannia glutinosa.It can lower blood glucose and improve IR,but its specific mechanism is not clear.Based on this,this topic intends to use liver cells(HepG 2)as the research object to explore the improvement effect and mechanism of AU on IR.First,through network pharmacology methods,predict the possible target of AU to improve IR,and verify the binding ability of AU to the target through molecular docking.The results showed that the possible targets for AU to improve IR are Akt1,interleukin-6(IL-6),insulin-like growth factor 1(IGF-1),peroxisome proliferation-activated receptor γ(PPARγ),tumor necrosis factor(TNF)and so on.Secondly,the MTT method was used to detect the cytotoxicity of AU to HepG 2.When the AU concentration reached 320 μmol/L,the cell viability was greater than 80% compared with the control group.Further experiments were performed on the AU treatment of HepG 2cell IR model group(IR-HepG 2).The drug concentration is 40,80,and 160 μmol/L.The glucose oxidase method was used to determine the effect of AU on the glucose consumption of IR cells,and found that AU can increase the glucose consumption of IR-HepG 2.Third,Western blotting detects the insulin receptor substrate/protein kinase B(IRS/Akt)insulin signaling pathway and the expression of glycogen synthesis key protein glycogen synthesis kinase 3β(GS3Kβ)phosphorylation and gluconeogenesis key protein fork head transcription The expression of factor 1(Fox O1),phosphoenolpyruvate carboxykinase(PEPCK)and glucose-6-phosphatase(G6Pase)was found to activate the IRS/Akt signaling pathway in IR-HepG 2 cells and increase the phosphorylation of GS3Kβ Expression;enhanced Fox O1 phosphorylation,reduced PEPCK and G6 Pase protein expression,proving that AU improves IR by increasing glycogen synthesis and weakening gluconeogenesis.Finally,the ELISA method was used to detect the effect of AU on IL-6 and TNF-α of IRHepG 2 cells.The results showed that AU has an inhibitory effect on the inflammatory factors IL-6 and TNF-α of IR-HepG 2 cells.The kit was used to detect the reactive oxygen content in IR-HepG 2 cells,and it was found that AU can reduce the reactive oxygen content in IR-HepG2 cells.In summary,AU has a certain improvement effect on IR.This effect may be achieved by activating the IRS/Akt signaling pathway,increasing glycogen synthesis,slowing down gluconeogenesis,and regulating the amount of inflammatory factors and ROS in IR-HepG 2cells.Provide a theoretical basis for further research on improving the effect of AU on IR.