Experimental Study of AMPK/IR/IRS1 Pathway Mediating the Mechanism of Myocardial Insulin Resistance in Diabetic Mice
10.3969/j.issn.1671-7414.2025.02.022
- VernacularTitle:AMPK/IR/IRS1通路介导影响糖尿病小鼠心肌胰岛素抵抗机制的实验研究
- Author:
Pu ZHANG
1
;
Jun ZHANG
;
Xuefeng LI
Author Information
1. 太和医院(湖北医药学院附属医院) 心血管疾病诊疗中心,湖北 十堰 442000
- Publication Type:Journal Article
- Keywords:
diabetes;
heart muscle;
AMPK/IR/IRS1 pathway;
insulin resistance;
oxidative stress
- From:
Journal of Modern Laboratory Medicine
2025;40(2):119-122,128
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the role and possible mechanism of adenosine monophosphate(AMP)-dependent protein kinase(AMPK)/insulin receptor(IR)/insulin receptor substrate(IRS1)pathway in myocardial insulin resistance in diabetic mice.Methods Thirty C57BL/6J mice were randomly divided into control group,diabetes group and AMPK-activated group according to the experimental design,with 10 mice in each group.Fasting blood glucose(FBG)was detected by a dynamic blood glucose detector detected.Glycosylated hemoglobin kit(HbA1c)was used to detect the level of HbA1c in mice.Fasting insulin(FINS)was detected by insulin detection kit in mice.Heart rate(HR),left ventricular end-systolic diameter(LVIDd),left ventricular end-diastolic diameter(LVIDs),ejection fraction(EF)and left ventricular fractional shortening(LVFS)were measured by echocardiography.Masson staining was used to detect myocardial collagen deposition in mice.The levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),glutathione(GSH),malondialdehyde(MDA)and reactive oxygen species(ROS)were detected by ELISA kit.The protein levels of AMPK,IR and IRS1 in myocardial tissue were detected by Western blotting(WB).RT-qPCR detected the mRNA levels of AMPK,IR and IRS1 in myocardial tissue.Results Compared with the control group,the levels of FBG,HbA1c,FINS,TC,TG and LDL-C in diabetic group were increased(t=14.94～63.46),the cardiac function indexes HR,EF and LVFS decreased(t=56.62,199.00,42.50),LVIDd increased(t=176.80),and the differences were statistically significant(all P<0.05),and there was no significant difference in LVIDs(t=3.46,P>0.05).The collagen deposition around small blood vessels in myocardial interstitial was increased,and the serum GSH level was decreased(t=5.75),ROS and MDA levels increased(t=22.60,15.18),the expression levels of AMPK,IR,IRS1 protein(t=7.00,4.33,3.66)and mRNA(t=2.61,5.17,6.79)in myocardial tissue decreased,and the differences were statistically significant(all P<0.05).Compared with diabetic group,the levels of FBG,HbA1c,FINS,TC,TG and LDL-C in AMPK activated group were decreased(t=9.14～56.34),the cardiac function indexes HR,EF and LVFS increased(t=135.90,152.00,41.99),LVIDd decreased(t=203.20),and the differences were statistically significant(all P<0.05),and there was no significant difference in LVIDs(t=1.58,P>0.05).Perivascular collagen deposition decreased and serum GSH level increased(t=19.60),ROS and MDA levels decreased(t=32.90,23.44),the expression levels of AMPK,IR,IRS1 protein(t=15.14,29.44,17.15)and mRNA(t=11.52,9.67,8.49)in myocardial tissue increased,and the differences were statistically significant(all P<0.05).Conclusion Activation of AMPK can improve the cardiac function structure,reduce blood glucose and lipid levels and reduce oxidative stress levels in diabetic mice.The mechanism of action may be related to insulin resistance mediated by AMPK/IR/IRS1 pathway.
