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Cardiac Insulin Resistance and MicroRNA Modulators英文文献资料.doc

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Cardiac Insulin Resistance and MicroRNA Modulators英文文献资料

HindawiPublishingCorporation ExperimentalDiabetesResearch Volume2012,ArticleID654904,12pages doi:10.1155/2012/654904 ReviewArticle CardiacInsulinResistanceandMicroRNAModulators LakshmiPulakat,1,2,3,4AnnayyaR.Aroor,1,3,4RukhsanaGul,1,3,4andJamesR.Sowers1,3,4,5 1 2 3 4 5 DepartmentofInternalMedicine,SchoolofMedicine,UniversityofMissouri,Columbia,MO65212,USA DepartmentofNutritionandExercisePhysiology,SchoolofMedicine,UniversityofMissouri,Columbia,MO65212,USA DiabetesandCardiovascularLaboratory,SchoolofMedicine,UniversityofMissouri,Columbia,MO65212,USA HarryS.TrumanMemorialVeterans’Hospital,Columbia,MO65201,USA DepartmentofMedicalPharmacologyandPhysiology,SchoolofMedicine,UniversityofMissouri,OneHospitalDrive, Columbia,MO65212,USA CorrespondenceshouldbeaddressedtoJamesR.Sowers,sowersj@ Received8July2011;Accepted22July2011 AcademicEditor:JunRen Copyright?2012LakshmiPulakatetal. This is an open access article distributed under the Creative Commons Attribution License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly cited. Cardiac insulin resistance is a metabolic and functional disorder that is often associated with obesity and/or the cardiorenal metabolic syndrome (CRS), and this disorder may be accentuated by chronic alcohol consumption. In conditions of over- nutrition,increasedinsulin(INS)andangiotensinII(AngII)activatemammaliantargetforrapamycin(mTOR)/p70S6kinase (S6K1) signaling, whereas chronic alcohol consumption inhibits mTOR/S6K1 activation in cardiac tissue. Although excessive activationofmTOR/S6K1inducescardiacINSresistanceviaserinephosphorylationofINSreceptorsubstrates(IRS-1/2),italso renderscardioprotectionviaincreasedAngIIreceptor2(AT2R)upregulationandadaptivehypertrophy.IntheINS-resistantand hyperinsulinemicZuckerobese(ZO)rat,arodentmodelforCRS,activationofmTOR/S6K1signalingincardiactissueisregulated byprotectivefeed-backmechanismsinvolvingmTOR?AT2Rsignalingloopandpro?lechangesofmicroRNAthattargetS6K