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1、组织特异性胰岛素抵抗及其代谢综合症的机制探讨郭绍东美国德克萨斯农工大学医学院医学系通讯作者 :ShaodongGuoDivisionofMolecularCardiologyDepartmentofMedicineCollegeofMedicineTexasA&MUniversityHealthScienceCenter261901South1stStreet,Bldg.205Temple,TX76504,USATel:254-743-1222Fax:254-743-0165（USA)Email:sguo@medi
2、cine.tamhsc.eduTissue-specificInsulinResistanceandAssociatedMechanismsfortheMetabolicSyndromeShaodongGuoAbstractMetabolicsyndromeisknownasinsulinresistancesyndromeandhasbecomeamajorpublichealthproblemworldwide.Itisrepresentedbyagroupofinterrelateddisorders,inc
3、ludingobesity,hyperglycemia,hyperinsulinemia,hyperlipidemia,andhypertension.Metabolicsyndromeisahighriskfactorfortype2diabetesmellitusandcardiovasculardiseases.Asthemostimportanthormoneinthebodyincontrolofenergyhomeostasis,insulinanditssignalingcascadenormally
4、controlcellgrowth,metabolismandsurvivalthroughactivationofmitogen-activatedproteinkinases(MAPK)andphosphotidylinositide-3-kinase(PI3K),ofwhichactivationofPI-3K-associatedwithinsulinreceptorsubstrate-1and-2(IRS1,2)andsubsequentAkt→Foxo1phosphorylationcascadehas
5、acentralroleincontrolofnutrienthomeostasisandorgansurvival.InactivationofAktandactivationofFoxo1,throughsuppressionIRS1andIRS2indifferentorgansfollowinghyperinsulinemia,metabolicinflammation,andovernutritionmayprovidetheunderlyingmechanismsformetabolicsyndrome
6、.TargetingtheIRS→Akt→Foxo1signalingcascadewilllikelyprovideastrategyfortherapeuticinterventioninthetreatmentoftype2diabetesanditscomplicationsinhumans.Thisreviewdiscusseshowadeficiencyofinsulinsignalingcomponentsindifferentorganscontributestothefeatureofthemet
7、abolicsyndrome.26EmphasiswillbeplacedontheroleofIRS1,IRS2,andassociatedsignalingpathwaysthatcoupletoAktandtheforkhead/wingedhelixtranscriptionfactorFoxo1.Keywords:Insulinresistance;metabolicsyndrome;insulinreceptorsubstrate-1,2;forkheadtranscriptionfactorFoxo1
8、ThisworkisfundedbyAmericanHeartAssociationgrantBGIA-7880040,AmericanDiabetesAssociationgrantJF-7-07-27,FacultyStart-upFundsfromtheTexasA&MUniversityHealthScienceCenter,andNIH/RO1DK
