安徽中医药大学学报2025，Vol.44Issue(3)：82-89,8.DOI:10.3969/j.issn.2095-7246.2025.03.017
地奥心血康调节IRS-1/PI3K/AKT信号通路改善肥胖小鼠胰岛素抵抗
Di'ao Xinxuekang Improves Insulin Resistance in Obese Mice by Regulating the Insulin Receptor Substrate-1/Phosphatidylinositol 3-kinase/Protein Kinase B Signaling Pathway
摘要
Abstract
Objective To investigate the mechanism of action of Di'ao Xinxiuekang(DXXK)in improving insulin resistance(IR)in obese mice.Methods A high-fat diet was used to establish a mouse model of obesity,and mice were randomly divided into normal group,model group,metformin group(150 mg/kg),and high-,middle-,and low-dose DXXK groups(200,60,and 20 mg/kg),with 10 mice in each group.The mice in the metformin group and the high-,middle-,and low-dose DXXK groups were given the corresponding drug by gavage,and those in the normal group and the model group were given an equal volume of normal saline by gavage,for 8 consecutive weeks.The mice were observed in terms of food intake,water intake,ac-tivity,body weight,Lee index,fat index,adipokine[leptin(LP),adiponectin(ADPN)],fasting blood glucose(FBG),fasting insulin(FINS),oral glucose tolerance test(OGTT),and intraperitoneal insulin tolerance test(ITT),and Homeostasis Model Assessment of Insulin Resistance(HOMA-IR)index and insulin sensitivity index(ISI)were calculated.HE staining was used to observe adipose tissue morphology.The 3T3-L1 mature cells were induced with dexamethasone to establish a cell model of IR,and the PI3K-specific inhibitor LY294002 and DXXK were used for intervention;lipid level and glucose consumption were measured.Western blot was used to measure the protein expression levels of the key proteins of the insulin receptor substrate-1(IRS-1)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and the downstream protein sterol regulatory element-binding protein-1c(SREBP-1c).Results There were no significant differences in the food intake,water in-take,and activity of mice between the model group and the high-,middle-,and low-dose DXXK groups(P＞0.05).There were significant reductions(P＜0.05)or a tendency of reduction(P＞0.05)in body weight,Lee index,fat index,leptin,FBG,FINS,HOMA-IR,the area under the OGTT curve,and the area under the ITT curve,and there were significant increa-ses(P＜0.05)or a tendency of increase(P＞0.05)in adiponectin and ISI.There was a reduction in the volume of adipocytes and an increase in the number of adipocytes,and there were significant increases(P＜0.05)or a tendency of increase(P＞0.05)in p-IRS-1/IRS-1,PI3K,and p-AKT/AKT in adipose tissue,while there was a significant reduction in the protein ex-pression level of SREBP-1c(P＜0.05).Compared with the DXXK group,the DXXK+LY294002 group showed significant in-creases(P＜0.05)or a tendency of increase(P＞0.05)in cell lipid content and the protein expression level of SREBP-1c,as well as significant reductions(P＜0.05)or a tendency of reduction(P＞0.05)in glucose uptake and the protein expression lev-el of PI3K and p-AKT/AKT.Conclusion DXXK can significantly improve IR in obese mice,possibly by regulating the IRS-1/PI3K/AKT signaling pathway and improving glucose and lipid metabolism.关键词
地奥心血康/IRS-1/PI3K/AKT信号通路/肥胖/胰岛素抵抗Key words
Di'ao Xinxuekang/Insulin receptor substrate-1/phosphatidylinositol 3-kinase/protein kinase B signaling pathway/Obesity/Insulin resistance分类
临床医学引用本文复制引用
尚慕鸿,王亚东,王昕,刘玉嫣,李国莺,陈光亮..地奥心血康调节IRS-1/PI3K/AKT信号通路改善肥胖小鼠胰岛素抵抗[J].安徽中医药大学学报,2025,44(3):82-89,8.基金项目
国家天然药物技术研究中心科研创新课题(XXK-E190105A) （XXK-E190105A）
安徽中医药大学校级探索性科研项目(AHUCM2024TS035) （AHUCM2024TS035）
