Re-Expression of IGF-II Is Important for Beta Cell Regeneration in Adult Mice 英文参考文献.docVIP

Re-Expression of IGF-II Is Important for Beta Cell Regeneration in Adult Mice 英文参考文献.doc

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Re-Expression of IGF-II Is Important for Beta Cell Regeneration in Adult Mice 英文参考文献

Re-ExpressionofIGF-IIIsImportantforBetaCell RegenerationinAdultMice LuxianZhou1.,StellaPelengaris2.,SylvieAbouna1,JamesYoung2,DavidEpstein3,JuliaHerold4 ,Tim WilhelmNattkemper4,HassanNakhai1,MichaelKhan2* 1SchoolofLifeSciences,UniversityofWarwick,Coventry,UnitedKingdom,2WarwickMedicalSchool,UniversityofWarwick,Coventry,UnitedKingdom,3Departmentof Mathematics,UniversityofWarwick,Coventry,UnitedKingdom,4BiodataMiningGroup,BielefeldUniversity,Bielefeld,Germany Abstract Background:Thekeyfactorswhichsupportre-expansionofbetacellnumbersafterinjuryarelargelyunknown.Insulin-like growthfactorII(IGF-II)playsacriticalroleinsupportingcelldivisionanddifferentiationduringontogenybutitsroleinthe adultisnotknown.InthisstudyweinvestigatedtheeffectofIGF-IIonbetacellregeneration. Methodology/PrincipalFindings:Weemployedaninvivomodelof‘switchable’c-Myc-inducedbetacellablation,pIns-c- MycERTAM,inwhich90%ofbetacellsarelostfollowing11daysofc-Myc(Myc)activationinvivo.Importantly,suchablation isnormallyfollowedbybetacellregenerationonceMycisdeactivated,enablingfunctionalstudiesofbetacellregeneration +/+ invivo.IGF-IIwasshowntobere-expressedintheadultpancreasofpIns-c-MycERTAM /IGF-II (MIG)mice,followingbeta cellinjury.AsexpectedinthepresenceofIGF-IIbetacellmassandnumbersrecoverrapidlyafterablation.Incontrast,in +/2 pIns-c-MycERTAM /IGF-II (MIGKO)mice,whichexpressnoIGF-II,recoveryofbetacellmassandnumbersweredelayedand impaired. Despite failure of beta cell number increase, MIGKO mice recovered from hyperglycaemia, although this was delayed. Conclusions/Significance:Ourresultsdemonstratethatbetacellregenerationinadultmicedependsonre-expressionof IGF-II, and supports the utility of using such ablation-recovery models for identifying other potential factors critical for underpinning successful beta cell regeneration in vivo. The potential therapeutic benefits of manipulating the IGF-II signalingsystemsmeritfurtherexploration. Citation:ZhouL,PelengarisS,AbounaS,YoungJ,EpsteinD,etal.(2012)Re-Exp

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