胰岛素抵抗与糖、脂代谢紊乱论文

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　　胰岛素抵抗与糖、脂代谢紊乱论文【关键词】胰岛素抵抗;脂代谢紊乱;糖代谢紊乱在众多心血管疾病的危险因素中胰岛素抵抗(Insulinresistance,IR)处于核心地位，IR可先于糖尿病及心血管疾病多年而存在。目前将胰岛素抵抗、中心性肥胖、糖耐量减低、高血压、血脂代谢紊乱等多种疾病的组合,统称为胰岛素抵抗综合征。尽管有很多遗传因素可诱导IR产生，但目前认为IR最主要的诱因是过量的糖和脂肪。高糖和高脂均能引起肌肉和脂肪组织的IR,高脂还能导致肝脏IR的产生。高脂喂养动物或者静脉输注高脂均能破坏葡萄糖的转运而迅速形成IR。血浆中脂类水平的升高,主要是游离脂肪酸(FFA)和甘油三酯(TG)、低密度脂蛋白胆固醇(LDL)含量增加是导致IR的重要原因〔1〕。2型糖尿病血糖过高会引起胰腺β细胞分泌胰岛素减少,高血糖本身还进一步导致IR〔2〕。现就IR与糖、脂代谢紊乱的关系综述如下。1脂代谢紊乱与IR1.1FFA升高与IRFFA是引起IR的最主要非激素物质之一，可通过多种方式干扰胰岛素的作用和葡萄糖代谢,能破坏胰岛素敏感组织中的胰岛素表达。肝脏高水平的FFA使肝糖异生和糖原分解增加,还抑制肝细胞对胰岛素的灭活〔3〕，同时，FFA能启动纤维蛋白原和纤溶酶原激活物抑制因子1(PAI1)在肝脏的合成〔4〕。在骨骼肌主要是抑制葡萄糖的摄取和氧化〔5〕。体内FFA长期升高还会耗竭胰岛β细胞的分泌，导致其凋亡。在脂肪组织中，FFA抑制脂蛋白脂酶的活性.freeletabolismintheetiologyoftype2diabetes〔J〕.Diabetes,2002;51(1)：718.2RossettiL,GiaccariA,DeFronzoRA.Glucosetoxicity〔J〕.DiabetesCare,1990;13：610.3SunY,LiuS,FergusonS,etal.Phosphoenolpyruvatecarboxykinaseoverexpressionselectivelyattenuatesinsulinsignalingandhepaticinsulinsensitivityintransgenicmice〔J〕.JBiolChem,2002;277:233017.4KittFP,GeraldIS.Etilogyofinsulinresistance〔J〕.AmJMed,2006;119(5A):s106.5YuC,ChenY,ClineGechanismbyuscle〔J〕.JBiolChem,2002;277:502306. 6BarbaraM,JanjaM,AndrejJ,etal.Molecularmechanismofinsulinresistanceandassociateddiseases〔J〕.ClinChimActa,2006;375:2035.7RandlePJ,Hales,GarlandPB,etal.Theglucosefattyacidcyde.Itsroleininsulinsensitivityandthemetabolicdisturbancesofdiabetesmellitus〔J〕.Lancet,1963;1:7859.8Yoshikaentofperoxisomeproliferatorsactivatedreceptorsαorpancreatic/duodenalhomeobox〔J〕.Metabolism,2001;50:6138.9GrundySM,HansenB,SmithSC,etal,ClinicalManagementofMetabolicSyndrome.ReportoftheAmericanHeartAssociation/NationalHeart,Lung,andBloodInstitute/AmericanDiabetesAssociationConferenceonscientificissuesrelatedtomanagement〔J〕.Circulation,2004;109:5516.10FerranniniE,HaffnerSM,MitchellBD,etal.Hyperinsulinaemia:thekeyfeatureofacardiovascularandmetabolicsyndrome〔J〕.Diabetologia,1991;34:41622.11KenhE,ajorpulmonaryembolism:revieodynamicallysignificantpulmonaryembolism〔J〕.Chest,2002;121:877905.12ArcasoySM,KreitJetabolism,2000;49(12):162731.14Eschetabolicsyndrome,insulinresistanceandincreasedcardiovascular(CV)morbidityandmortalityintype2diabetes:aetiologicalfactorsinthedevelopmentofCVplications〔J〕.DiabetesMetab,2003;29(4Pt2);S1927.15AbbasiF,BroendolaC,etal.RelationshipbetCollCardiol,2002;40:93743.16HamelE,PacouretG,VincentelliD,etal.Thrombolysisorheparintherapyinmassivepulmonaryembolisma128patientmonocenterregistry〔J〕.Chest,2001;120:1205.17SohneM,ten,BullerHR.Biomarkersinpulmonaryembolism〔J〕.CurrOpinCardiol,2004;19:55862. 18KonstantinidesS,TiedeN,teGeibelA,etal.parisionofalteplaseversusheparnforresolutionofmajorpulmonaryembolism〔J〕.AMJCardiol,1998;82:96670.19McRaeSJ,GinsbergJS.Initialtreatmentofvenousthromboembolism〔J〕.Circulation,2004;110:s39.20吴正,姜月华.脂毒性和2型糖尿病关系探讨〔J〕.现代中西医结合杂志,2004;13(20):27934.21朱姿英,薛耀明.高甘油三酯血症和2型糖尿病〔J〕.中国糖尿病杂志,2003;11(2):1534.22沈彦,方水林,袁静平.控制血糖对2型糖尿病脂质代谢紊乱的影响〔J〕.浙江中西医结合杂志,2004;14(11):6812.23GrundySM,BreanJI,etal.Definitionofmetabolicsyndrome:reportoftheNationalHeart,Lung,andBloodInstituteAmericanHeartAssociationconferenceonscientificissuesrelatedtodefinition〔J〕.ArteriosclerThrombVascBiol,2004;24(2):138.24MarshallS,BacoteV,TraxingerRR.Discoveryofametabolicpathediatingglucoseinduceddesensitizationoftheglucosetransportsystem〔J〕.JBiolChem,1991;266:4706.25VerenaKL.Highglucoseinducedtransforminggroediatedbythehexosaminepatherularmesangialcells〔J〕.JClinInvest,1998;101:160.26OkiT,YamazakiK,KuromitsuJ,etal.cDNAcloningandmappingofanovelsubtypeofglutamine:fructose6phosphateamidotransferase(GFAT2)inhumanandmouse〔J〕.Genomics,1999;57(2):227.