目的:探讨有氧运动与膳食干预对胰岛素抵抗(IR)大鼠胰岛β细胞LKB1/AMPK信号的影响,进一步阐明有氧运动与膳食干预改善IR的中心机制.方法:采用10w高脂膳食喂养的方法建立IR大鼠模型,建模成功后随机分为高脂膳食组(IRHC)、高脂膳食运动组(IRHE)、普通膳食组(IRNC)、普通膳食运动组(IRNE);正常大鼠随机分为安静对照组(NC)和单纯运动组(NE).运动组大鼠进行中等强度有氧运动,跑台速度为20 m/min,坡度0%,60 min/d,5 d/w,共计8 w.末次运动后24 h,禁食12 h后麻醉处死并取材.测定空腹血糖(FBG)、空腹胰岛素(FINS)、C肽、肿瘤抑制因子(LKB1)、腺苷蛋白激酶(AMPKα)蛋白和磷酸化表达.结果:1)10 w高脂膳食喂养后大鼠与普通膳食组相比体重、FBG、FINS、Homa-IR均显著升高(均P<0.01),Homa-ISI显著下降(P<0.01).2)有氧运动与膳食干预8 w后对IR大鼠的影响:与NC组相比,NE组大鼠体重、FBG、C肽显著降低(P<0.05-0.01),胰岛β细胞p-AMPKαThr172表达显著升高(P<0.05).与IRHC组相比,IRHE组和IRNE组大鼠体重、FBG、FINS、C肽、Homa-IR均显著降低(P<0.05-0.01)、Homa-ISI均显著升高(P<0.05-0.01),IRNC组大鼠体重、C肽均显著降低(P<0.01).与IRHC组相比,IRNC组和IRNE组大鼠胰岛β细胞LKB1、AMPKα、p-AMPKαThr172蛋白表达均显著升高(P<0.05-0.01).结论:长期高脂膳食可降低胰岛β细胞LKB1/AMPK信号蛋白表达,促进胰岛素分泌;8 w膳食干预可增加IR大鼠胰岛β细胞LKB1/AMPK信号蛋白表达,减少胰岛素分泌.%Objective:To investigate the impact of aerobic exercise and diet intervention on LKB1/AMPK Signal in the islet β cell of insulin resistance rats.Methods:High-fat diet-induced insulin resistance rats were randomly divided into high-fat diet sedentary control group(IRHC),high-fat diet exercise group(IRHE)and normal diet sedentary group(IRNC),normal diet exercise group(IRNE).The normal rats were randomly divided into sedentary control group(NC)and exercise group(NE).Rats in all exercise groups underwent a moderate intensity treadmill(20m/min,0%,60 min/d,5d/w)for 8 weeks.The blood in abdominal aorta and islet were collected after 12h fasting,FBG,FINS,C-peptide,LKB1,AMPKα and p-AMPKαThr172 were measured.Results:1.Compared with the control group,the body weight,FPG level,FINS and HOMA-IR of IRHE significantly increased after 10 weeks(all P<0.01),Homa-ISI significantly decreased(P<0.01).2.The effect of aerobic exercise and diet changed.Compared with NC,the body weight,FBG and C-peptide of rats in NE significantly decreased(P<0.05-0.01) and the protein expression of p-AMPKαThr172 in islet β cell significantly increased(P<0.05).Compared with IRHC,the body weight,FBG,FINS,C-peptide and Homa-IR(P<0.05-0.01)of rats in IRHE and IRNE significantly decreased and Homa-ISI significantly increased(P<0.05-0.01);The body weight and C-peptide significantly decreased(P<0.01).The protein expression of LKB1,AMPKα and p-AMPKαThr172(P<0.05-0.01)in islet β cell of rats in IRNC and IRNE significantly increased.Conclusions:Long-term high-fat diet can reduce the expression of LKB1/AMPK in pancreatic β-cell,leading to promote insulin secretion.The restoration of normal diet can increase the expression of LKB1/AMPK in pancreatic β-cell,decrease insulin secretion.
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