Metabolic Regulation in Progression to Autoimmune Diabetes 英文参考文献.docVIP

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Metabolic Regulation in Progression to Autoimmune Diabetes 英文参考文献.doc

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Metabolic Regulation in Progression to Autoimmune Diabetes 英文参考文献

MetabolicRegulationinProgressiontoAutoimmune Diabetes MarkoSysi-Aho1,AndreyErmolov2,PeddintiV.Gopalacharyulu1,AbhishekTripathi3¤ ,Tuulikki Seppa¨nen-Laakso1,JohannaMaukonen1,IsmoMattila1,SuviT.Ruohonen4,LauraVa¨ha¨talo4 ,Laxman Yetukuri1,TainaHa¨rko¨nen5,ErnoLindfors1,JanneNikkila¨6,JormaIlonen7,8,OlliSimell9,MariaSaarela1, MikaelKnip5,10,11,SamuelKaski2,3,EriikaSavontaus4,12,MatejOresˇicˇ1,13 * 1VTTTechnicalResearchCentreofFinland,Espoo,Finland,2AaltoUniversitySchoolofScience,DepartmentofInformationandComputerScience,HelsinkiInstitutefor Information Technology HIIT, Espoo, Finland, 3Helsinki Institute for Information Technology HIIT, Department of Computer Science, University of Helsinki, Finland, 4DepartmentofPharmacology,DrugDevelopmentandTherapeutics,UniversityofTurku,Turku,Finland,5HospitalforChildrenandAdolescents,UniversityofHelsinki, Helsinki, Finland, 6Finnish Red Cross Blood Service, Helsinki, Finland, 7Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland, 8ImmunogeneticsLaboratory,UniversityofTurku,Turku,Finland,9DepartmentofPediatrics,UniversityofTurku,Turku,Finland,10DepartmentofPediatrics,Tampere University Hospital, Tampere, Finland, 11Folkha¨lsan Research Center, Helsinki, Finland, 12Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland, 13InstituteofMolecularMedicineFinlandFIMM,Helsinki,Finland Abstract Recentevidencefromserummetabolomicsindicatesthatspecificmetabolicdisturbancesprecedeb-cellautoimmunityin humansandcanbeusedtoidentifythosechildrenwhosubsequentlyprogresstotype1diabetes.Themechanismsbehind thesedisturbancesareunknown.Hereweshowthespecificityofthepre-autoimmunemetabolicchanges,asindicatedby theirconservationinamurinemodeloftype1diabetes.Weperformedastudyinnon-obeseprediabetic(NOD)micewhich recapitulatedthedesignofthehumanstudyandderivedthemetabolicstatesfromlongitudinallipidomicsdata.Weshow that female NOD mice who later progress to autoimmune diabetes exhibit the same lipidomic patt