Effect of Taxifolin on Oxidative Stress and Pancreatic Islet Function in Diabetes Model Rats by Regulating PI3K/AKT/mTOR Pathway
Objective:To explore the impacts of taxifolin(TAX)on oxidative stress and pancreatic islet function in diabetes model rats by regulating phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway.Methods:One hundred and two Sprague-Dawley(SD)rats without specific pathogen(SPF)were randomly divided into Model group,TAX low-dose group(5 mg/kg),TAX medium-dose group(10 mg/kg),TAX high-dose group(20 mg/kg)and,PI3K activator group(0.02 mg/kg PI3K activator 740Y-P+20 mg/kg TAX),mTOR activator group(10 mg/kg mTOR activator MHY1485+20 mg/kg TAX),with 12 rats in each group.In addition,with 12 normal rats were selected as Control group.The body mass of each rat was measured.Fasting blood glucose(FBG),glucose tolerance test(OGTT)and fasting insulin(FINS)were measured.Homeostasis model assessment-IR(HOMA-IR),pancreatic isletβcell function index(HOMA-β)and insulin sensitivity index(ISI)were calculated.Hematoxylin-eosin(HE)staining was used to observe the pancreatic tissue injury of rats,and the number of islets was calculated.The serum levels of total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),and free fatty acid(FFA)were detected.Serum malondialdehyde(MDA),reactive oxygen species(ROS),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)levels were detected by the kit.Western Blot was used to detect the expression of PI3K/AKT/mTOR pathway protein in rat pancreas.Results:Compared with the Control group,body mass,FBG,OGTT(0.5,1.0,2.0 h)blood glucose,FINS,HOMA-IR,TC,TG,LDL-C,FFA,ROS,MDA,p-PI3K/PI3K,p-AKT/AKT,p-mTOR/mTOR increased in Model group,ISI,HOMA-β,HDL-C,GSH-Px,SOD,islet number decreased(P<0.05).Compared with Model group,body mass,FBG,OGTT(0.5,1.0,2.0 h)blood glucose,FINS,HOMA-IR,TC,TG,LDL-C,FFA,ROS,MDA,p-PI3K/PI3K,p-AKT/AKT,p-mTOR/mTOR levels of rats in TAX low-dose group,TAX medium-dose group and TAX high-dose group decreased,ISI,HOMA-β,HDL-C,GSH-Px,SOD,and islets increased(P<0.05).Both PI3K and mTOR activators attenuated the improvement effect of high dose TAX on diabetic model rats(P<0.05).Conclusion:TAX could inhibit STZ-induced oxidative stress in diabetic model rats and improve pancreatic islet function by inhibiting PI3K/AKT/mTOR signaling pathway.
diabetesoxidative stressTaxifolinphosphatidylinositol 3-kinase/serine-threonine kinase B/mammalian target of rapamycin pathwaypancreatic islet functionexperimental study
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