Fermentation, Isolation, Structure, and antidiabetic activity of NFAT-133 produced by Streptomyces strain PM0324667.docVIP

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Fermentation, Isolation, Structure, and antidiabetic activity of NFAT-133 produced by Streptomyces strain PM0324667.doc

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Kulkarni-Almeidaetal.AMBExpress2011,1:42 /content/1/1/42 ORIGINAL OpenAccess Fermentation,Isolation,Structure,and antidiabeticactivityofNFAT-133producedby StreptomycesstrainPM0324667 AshaAKulkarni-Almeida1*,ManojaKBrahma1,PrabhuPadmanabhan1,PrabhuDMishra1,RajashriRParab1, NitinVGaikwad1,ChandniSThakkar1,PradiptaTokdar1,PrafullVRanadive1,AmruthaSNair1,AnaghaADamre1, UmakantABahirat1,NitinJDeshmukh1,LalitSDoshi1,AmolVDixit1,SajiDGeorge1,RamAVishwakarma2, KumarVSNemmani1andGirishBMahajan1* Abstract Type-2diabetesismediatedbydefectsineitherinsulinsecretionorinsulinaction.Inanefforttoidentifyextracts thatmaystimulateglucoseuptake,similartoinsulin,ahighthroughput-screeningassayformeasuringglucose uptakeinskeletalmusclecellswasestablished.Duringthescreeningstudiestodiscovernovelantidiabetic compoundsfrommicrobialresourcesaStreptomycesstrainPM0324667(MTCC5543,theStrainaccessionnumberat InstituteofMicrobialTechnology,Chandigarh,India),anisolatefromaridsoilwasidentifiedwhichexpresseda secondarymetabolitethatinducedglucoseuptakeinL6skeletalmusclecells.Byemployingbioactivityguided fractionationtechniques,atri-substitutedsimplearomaticcompoundwithanti-diabeticpotentialwasisolated.It wascharacterizedbasedonMSand2DNMRspectraldataandidentifiedasNFAT-133whichisaknown immunosuppressiveagentthatinhibitsNFAT-dependenttranscriptioninvitro.Ourinvestigationsrevealedthe antidiabeticpotentialofNFAT-133.ThecompoundinducedglucoseuptakeindifferentiatedL6myotubeswithan EC50 of6.3±1.8μMwithoutactivatingtheperoxisomeproliferator-activatedreceptor-g.Further,NFAT-133was alsoefficaciousinvivoindiabeticanimalsandreducedsystemicglucoselevels.Thusitisapotentiallead compoundwhichcanbeconsideredfordevelopmentasatherapeuticforthetreatmentoftype-2diabetes.We havereportedherewiththeisolationoftheproducermicrobe,fermentation,purification,invitro,andinvivo antidiabeticactivityofthecompound. Keywords:NFAT-133,Streptomycessp.,Antidiabetic,Actinomycetes Background Howevertheyareunabletoachieverelieffromdiabete