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

Effectsofexercisecombinedwithdietcontrolonglucosemetabolism，developmentofinsulinresistance，andbloodlipidmetabolisminratswithtype2diabetes

摘要:

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（fastbloodglocuse，FBG）、血清胰岛素（fastinsulin，FINS）、甘油三酯（triglycerides，TG）、胆固醇（cholesterol，TC）和低密度脂蛋白-胆固醇（lowdensitylipoproteincholesterol，LDL-C），进行葡萄糖耐量实验（glucosetolerancetest，GTT）及胰岛素耐量实验（insulintolerancetest，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（glucosekinase，GK）及三磷酸腺苷（adenosinetriphosphate，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mTORmRNA的表达，采用Westernblot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、PKBmRNA均较模型对照组大鼠明显增加，mTORmRNA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。

Abstract:

Objective：Toinvestigatetheeffectsofexercisecombinedwithdietcontrolonglucosemetabolism，developmentofinsulinresistance，andbloodlipidmetabolisminratswithtype2diabetes.Methods：Atotalof35Wistarratswereincludedinthisstudy.TenWistarratswererandomlyselectedasnormalcontrolgroup，andtheremaining25ratswereusedtoestablishatype2diabetesmodel.Atotalof20modelratswererandomlydividedintomodelcontrolgroupandintervention（exercisecombinedwithdietcontrol）group.Theratsinthenormalcontrolgroupwerefreetomoveandgivenstandardfeed.Theratsinthemodelcontrolgroupwerefreetomoveandgivenhigh-fatandhigh-sugardiet.Swimmingtrainingandstandardfeedweregiventotheratsintheinterventiongroup.Theinterventionperiodinthethreegroupswas8weeks.Bodyweightanddailyfoodintakeoftheratsinthethreegroupsweremeasuredbeforeexperiment，aftermodelingandbeforeintervention，andafter4and8weeksofintervention.Beforeinterventionandafter8weeksofintervention，thelevelsoffastingbloodglucose（FBG），fastinginsulin（FINS），triglyceride（TG），cholesterol（TC），andlow-densitylipoproteincholesterol（LDL-C）weremeasured，andglucosetolerancetest（GTT）andinsulintolerancetest（ITT）wereperformedtoassessinsulinresistance.Afterexercise，thepancreatictissuewastakentodeterminetheactivitiesofglucoseki－nase（GK）andadenosinetriphosphatase（ATPase）；themRNAexpressionofinsulinreceptorsubstrate-1（IRS-1），phosphoinositide3-kinase（PI3K），proteinkinaseB（PKB），andmammaliantargetofrapamycin（mTOR）inthepancreatictissuewasdeterminedbyreal-timepolymerasechainreaction；theproteinexpressionofIRS-1，phosphorylatedIRS-1（p-IRS-1），PI3K，PKB，phosphorylatedPKB（p-PKB），mTOR，andphosphorylatedmTOR（p-mTOR）inthepancreatictissuewasdeterminedbyWesternblot.Results：①After4and8weeksofintervention，theinterventiongrouphadasignificantlyhigherbodyweightthanthemodelcontrolgroup（P<0.05），andtherewasasignificantdifferenceindailyfoodintakebetweenthetwogroups（P<0.05）.②After8weeksofintervention，theinterventiongrouphadsignificantlylowerlevelsofFBGandFINS，homeostasismodelassessmentofinsulinresistance，areaunderthereceiveroperatingcharacteristiccurve（AUC）GTT，andAUCITTthanthemodelcontrolgroup（P<0.05）.③After8weeksofinterven－tion，theinterventiongrouphadsignificantlylowerlevelsofTG，TC，andLDL-Cthanthemodelcontrolgroup（P<0.05）.④After8weeksofintervention，theinterventiongrouphadsignificantlyhigherGKandATPaseactivitiesinthepancreatictissuecomparedwiththemodelcontrolgroup（P<0.05）.⑤After8weeksofintervention，theinterventiongrouphadsignificantlyhighermRNAexpressionofIRS-1，PI3K，andPKBinthepancreatictissueandsignificantlylowermRNAexpressionofmTORinthepancreatictissuecomparedwiththemodelcontrolgroup（P<0.05）.⑥After8weeksofintervention，theinterventiongrouphadsignificantlyhigherproteinexpressionofIRS-1，p-IRS-1，PI3K，PKB，andp-PKBinthepancreatictissueandsignificantlylowerproteinexpressionofmTORandp-mTORcomparedwiththemodelcontrolgroup（P<0.05）.Conclusion：Exercisecombinedwithdietcontrolcancontrolthebloodglucoselevelofratswithtype2diabetes，alleviateinsulinresistanceanddyslipidemia，increasetheactivitiesofGKandATPaseinthepancreatictissue，andregulatetheIRS/PI3K-Aktsignalingpathway.