糖尿病英语文献

ReviewRevie–December2013;©2013LandesBioscienceIntroductionSincethediscoveryofitsantirachiticeffectinthe1920s,thesunshinevitaminwasformanyyearsonlyseeninrelationtoitsfunctionincalciumandbonemetabolism.AvarietyofresearchresultsfromrecentyearshaveshownthatvitaminDinitshormonallyactiveform,1α,25-dihydroxyvitaminD[1α,25(OH)2D;calcitriol]isnotonlyaregulatorofcalciumandphosphatehomeostasis,buthasnumerousextra-skeletaleffects.TheseincludethesignificantimpactofthevitaminDhormoneonthecardiovascularsystem,centralnervoussystem,endocrinesystemandimmunesystemaswellasoncelldifferentiationandcellgrowth.1,21α,25(OH)2Dmanifestsitsdiversebiologicaleffects(endo-crine,autocrine,paracrine)bybindingtothevitaminDreceptor(VDR)foundinmostbodycells(Fig.1).VitaminDreceptorshavebeenfoundinover35targettissuesthatarenotinvolvedinbonemetabolism.Theseincludeendothelialcells,isletcellsofthepancreas,hematopoieticcells,cardiacandskeletalmusclecells,monocytes,neurons,placentalcellsandT-lymphocytes.ItisestimatedthatVDRactivationmayregulatedirectlyand/orindirectlyaverylargenumberofgenes(0.5–5%ofthetotalhumangenomei.e.,100–1250genes).4ThefactthatthevitaminDreceptorisexpressedbymanytissuesresultsinthepronouncedpleiotropiceffectofvitaminDhormone.1-5FromSunshineVitamintoSunshineHormoneVitaminD—thesunshinevitamin—isformedintheskinfrom7-dehydrocholesterol(7-DHC)viatheintermediateprevi-taminD3andwiththehelpofsunlight(UVB:290–315nm).PrevitaminD3isconvertedbybodyheattovitaminD3[chole-calciferol].ExcessivesunlightexposuredegradesprevitaminD3andvitaminD3toinactivephotoproducts,thuspreventingexces-siveproductionofthesunshinevitaminintheskin.TheliverconvertsvitaminD3viatheenzyme25-hydroxylase(25-OHase:CYP27A1,CYP2R1)into25-hydroxyvitaminD[25(OH)D],alsoknownascalcidiol.ThemitochondrialCYP27A1andmicrosomalCYP2R1arethetwomajorenzymesinvolvedinthehydroxylationatC-25,althoughthereareseveralCYPenzymesthatshow25-hydroxylase(25-OHase)activitybutwithhigherKmandlowerVmax.Serum25(OH)D(1ng/mL=2,5nmol/L)isthebarometerforthemedicallaboratoryevaluationofthevita-minDstatus.1-325(OH)Disthenconvertedinthekidneysviatheenzyme25-hydroxyvitaminD-1-α-hydroxylasealsoknownascyto-chromep45027B1(1-OHase:CYP27B1)intothemetabolicallyactivevitaminDhormone[1α,25(OH)2D].Thisenzymeisalsocalledrenal1-α-hydroxylase–sinceitoccursinthekidneys(→endocrineeffect).Therenalsynthesisof1,25(OH)2Disregulatedbyseveralfactorsincludingserumphosphorus,calcium,fibro-blastgrowthfactor23(FGF-23),parathyroidhormone(PTH)anditself.3Besidesthekidneys,amultitudeoftissueshavealocal1-α-hydroxylase(1-OHase)includingbone,placenta,prostate,keratinocytes,macrophages,T-lymphocytes,dendriticcells,sev-eralcancercells,andtheparathyroidgland.Dependingontheavailabilityof25(OH)Dandtheamountsrequired,thesecellscanproducethebiologicallyactivevitaminDhormonewiththe*Correspondenceto:UweGröber;Email:[e-mail]:07/15/2013;Revised:10/07/2013;Accepted:10/08/2013:Update2013FromricketsprophylaxistogeneralpreventivehealthcareUweGröber1,JörgSpitz2,JörgReichrath3,KlausKisters1,4,andMichaelFHolick51AcademyforMicronutrientMedicine;essen,Germany;2instituteforMedicalinformationandPrevention;wiesbaden,Germany;3UniversitätsklinikumdesSaarlandes;Homburg/Saar,Germany;4St.AnnaHospital,MedicalClinici;Herne,Germany;5BostonUniversityMedicalCenter;Boston,MAUSA;Keywords:vitaminD,25-hydroxyvitaminD,vitaminDdeficiency,osteoporosis,geneexpression,cardiovasculardiseases,hypertension,diabetesmellitus,autoimmunediseases,degenerativebraindisease,respiratorytractinfection,atopicdermatitis,cancer,drugsvitaminDhasreceivedalotofattentionrecentlyasaresultofameteoricriseinthenumberofpublicationsshowingthatvitaminDplaysacrucialroleinaplethoraofphysiologicalfunc-tionsandassociatingvitaminDdeficiencywithmanyacuteandchronicillnessesincludingdisordersofcalciummetabo-lism,autoimmunediseases,somecancers,type2diabetesmellitus,infectiousdiseasesandcardiovasculardisease.TherecentdataonvitaminDfromexperimental,ecological,case-control,retrospectiveandprospectiveobservationalstudies,aswellassmallerinterventionstudies,aresignificantandcon-firmthesunshinevitamin’sessentialroleinavarietyofphysio-logicalandpreventativefunctions.TheresultsofthesestudiesjustifytherecommendationtoimprovethegeneralvitaminDstatusinchildrenandadultsbymeansofahealthyapproachtosunlightexposure,consumptionoffoodscontainingvita-minDandsupplementationwithvitaminDpreparations.ingeneral,closerattentionshouldthereforebepaidtovitaminDdeficiencyinmedicalandpharmaceuticalpracticethanhasbeenthecasehitherto.e2-332Dermato-endocrinologyvolume5issue3helpoftheirlocal1-OHase(→autocrineandparacrineeffect).1α,25(OH)2Dislikethesexhormones(e.g.,estradiol)andcor-ticosteroids(e.g.,cortisone),whichareallsteroidhormones.2,4,5Viaafeedbackmechanism,the1α,25(OH)2Dlevelregulatesthesynthesisof1α,25(OH)2Dandreducesthesynthesisandsecre-tionofparathyroidhormoneintheparathyroidglands(Fig.1).1