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《2014-The search for the mechanism of early sympathetic islet》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。
1、NIHPublicAccessAuthorManuscriptDiabetesObesMetab.Authormanuscript;availableinPMC2015September01.NIH-PAAuthorManuscriptPublishedinfinaleditedformas:NIH-PAAuthorManuscriptNIH-PAAuthorManuscriptDiabetesObesMetab.2014September;16(01):96–101.doi:10.1111/dom.12341
2、.Thesearchforthemechanismofearlysympatheticisletneuropathy(eSIN)inautoimmunediabetesGeraldJ.TaborskyJr.1,2,QiMei2,DarylJ.Hackney3,andThomasO.Mundinger2GeraldJ.Taborsky:taborsky@u.washington.edu1DivisionofEndocrinology/Metabolism,VeteransAffairsPugetSoundHeal
3、thCareSystem,1660S.ColumbianWay,Seattle,WA98108USA2DivisionofEndocrinology,MetabolismandNutrition,DepartmentofMedicine,UniversityofWashington,Seattle,WA98109USA3SeattleInstituteforBiomedicalandClinicalResearch,1660S.ColumbianWay,Seattle,WA98108USAAbstractThi
4、sreviewoutlinesoursearchforthemechanismcausingtheearlylossofisletsympatheticnervesinautoimmunediabetes.Sinceourpreviousworkhasdocumentedtheimportanceofautonomicstimulationofglucagonsecretionduringhypoglycaemia,thelossofthesenervesmaycontributetotheknownimpai
5、rmentofthisspecificglucagonresponseearlyinhumantype1diabetes.Wethereforebrieflyreviewthecontributionthatautonomicactivation,andsympatheticneuralactivationinparticular,makestothesubsequentglucagonresponsetohypoglycaemia.Wealsodetailevidencethatanimalmodelsofa
6、utoimmunediabetesmimicboththeearlylossofisletsympatheticnervesandtheimpairedglucagonresponseseeninhumantype1diabetes.Usingdatafromtheseanimalmodels,weexaminemechanismsbywhichthislossofisletnervescouldoccur.Weprovideevidencethatitisnotduetodiabetichyperglycae
7、mia,butitisrelatedtothelymphocyticinfiltrationoftheislet.Ablatingthep75neurotrophinreceptor,whichispresentonsympatheticaxons,preventseSIN,but,interestingly,notdiabetes.Thus,weappeartohaveseparatedtheimmune-relatedlossofisletsympatheticnervesfromtheimmune-med
8、iateddestructionofisletβ-cells.Finally,wespeculateonawaytorestorethesympatheticinnervationoftheislet.KeywordsSympathetic;Neuropathy;P75neurotrophinreceptor;Hypoglycaemia;Type1diabetes;GlucagonCL
