运动锻炼联合膳食控制对2型糖尿病大鼠糖代谢、胰岛素抵抗形成和血脂代谢的影响

Effects of exercise combined with diet control on glucose metabolism,development of insulin resistance,and blood lipid metabolism in rats with type 2 diabetes

目的:研究运动锻炼联合膳食控制对2型糖尿病大鼠糖代谢、胰岛素抵抗和血脂代谢的影响。方法:35只Wistar大鼠随机取10只作为正常对照组,其余25只建立2型糖尿病模型,选择建模成功的20只大鼠随机分为模型对照组和运动联合膳食干预组。正常对照组大鼠自由活动、给予标准饲料;模型对照组大鼠自由活动、给予高脂高糖饲料;运动联合膳食干预组大鼠给予游泳训练、给予标准饲料。3组大鼠的干预期均为8周。分别于试验开始前、造模后运动锻炼前、运动4周和运动8周测定各组大鼠体质量和每日摄食量。分别于运动锻炼前及运动锻炼8周测定各组大鼠空腹血糖(fast blood glocuse,FBG)、血清胰岛素(fast insulin,FINS)、甘油三酯(triglycerides,TG)、胆固醇(cholesterol,TC)和低密度脂蛋白-胆固醇(low density lipoprotein cholesterol,LDL-C),进行葡萄糖耐量实验(glucose tolerance test,GTT)及胰岛素耐量实验(insulin tolerance test,ITT)评估胰岛素抵抗情况。运动锻炼结束后取胰腺组织测定葡萄糖激酶(glucose kinase,GK)及三磷酸腺苷(adenosine triphosphate,ATP)酶活性,采用实时聚合酶链反应定量(RT-PCR)检测胰腺组织IRS-1、PI3K、PKB和mTOR mRNA的表达,采用Western blot测定胰腺组织IRS-1、p-IRS-1、PI3K、PKB、p-PKB、mTOR和p-mTOR的蛋白表达。结果:①干预4周和8周时膳食运动干预组大鼠体质量较模型对照组明显增加、每日摄食量差异显著(P<0.05)。②8周干预后运动膳食干预组大鼠FBG、FINS、HOMA-IR、AUCGTT和AUCITT均较模型对照组大鼠明显降低(P<0.05)。③8周干预后运动膳食干预组大鼠TG、TC和LDL-C均较模型对照组大鼠明显降低(P<0.05)。④经过8周干预后运动膳食干预组大鼠胰腺组织GK和ATP酶活性均较模型对照组大鼠明显增加(P<0.05)。⑤经过8周干预后运动膳食干预组大鼠胰腺组织IRS-1、PI3K、PKB mRNA均较模型对照组大鼠明显增加,mTOR mRNA较模型对照组明显降低(P<0.05)。⑥经过8周干预后运动膳食干预组大鼠胰腺组织IRS-1、p-IRS-1、PI3K、PKB和p-PKB蛋白均较模型对照组大鼠明显增加,mTOR和p-mTOR蛋白较模型对照组明显降低(P<0.05)。结论:运动锻炼联合膳食控制可控制2型糖尿病大鼠的血糖,改善胰岛素抵抗,调节血脂紊乱,增加胰腺组织GK和ATP酶活性,并且对IRS/PI3K-Akt信号通路具有调节作用。

Objective:To investigate the effects of exercise combined with diet control on glucose metabolism,development of insulin resistance,and blood lipid metabolism in rats with type 2 diabetes.Methods:A total of 35 Wistar rats were included in this study.Ten Wistar rats were randomly selected as normal control group,and the remaining 25 rats were used to establish a type 2 diabetes model.A total of 20 model rats were randomly divided into model control group and intervention(exercise combined with diet control)group.The rats in the normal control group were free to move and given standard feed.The rats in the model control group were free to move and given high-fat and high-sugar diet.Swimming training and standard feed were given to the rats in the intervention group.The intervention period in the three groups was 8 weeks.Body weight and daily food intake of the rats in the three groups were measured before experiment,after modeling and before intervention,and after 4 and 8 weeks of intervention.Before intervention and after 8 weeks of intervention,the levels of fasting blood glucose(FBG),fasting insulin(FINS),triglyceride(TG),cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)were measured,and glucose tolerance test(GTT)and insulin tolerance test(ITT)were performed to assess insulin resistance.After exercise,the pancreatic tissue was taken to determine the activities of glucose kinase(GK)and adenosine triphosphatase(ATPase);the mRNA expression of insulin receptor substrate-1(IRS-1),phosphoinositide 3-kinase(PI3K),protein kinase B(PKB),and mammalian target of rapamycin(mTOR)in the pancreatic tissue was determined by realtime polymerase chain reaction;the protein expression of IRS-1,phosphorylated IRS-1(p-IRS-1),PI3K,PKB,phosphorylated PKB(p-PKB),mTOR,and phosphorylated mTOR(p-mTOR)in the pancreatic tissue was determined by Western blot.Results:①After 4 and 8 weeks of intervention,the intervention group had a significantly higher body weight than the model control group(P<0.05),and there was a significant difference in daily food intake between the two groups(P<0.05).②After 8 weeks of intervention,the intervention group had significantly lower levels of FBG and FINS,homeostasis model assessment of insulin resistance,area under the receiver operating characteristic curve(AUC)GTT,and AUCITT than the model control group(P<0.05).③After 8 weeks of intervention,the intervention group had significantly lower levels of TG,TC,and LDL-C than the model control group(P<0.05).④After 8 weeks of intervention,the intervention group had significantly higher GK and ATPase activities in the pancreatic tissue compared with the model control group(P<0.05).⑤After 8 weeks of intervention,the intervention group had significantly higher mRNA expression of IRS-1,PI3K,and PKB in the pancreatic tissue and significantly lower mRNA expression of mTOR in the pancreatic tissue compared with the model control group(P<0.05).⑥After 8 weeks of intervention,the intervention group had significantly higher protein expression of IRS-1,p-IRS-1,PI3K,PKB,and p-PKB in the pancreatic tissue and significantly lower protein expression of mTOR and p-mTOR compared with the model control group(P<0.05).Conclusion:Exercise combined with diet control can control the blood glucose level of rats with type 2 diabetes,alleviate insulin resistance and dyslipidemia,increase the activities of GK and ATPase in the pancreatic tissue,and regulate the IRS/PI3K-Akt signaling pathway.