资源描述：
《Leptin revisited its mechanism of action and potential for treating diabetes.pdf》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、REVIEWSLeptinrevisited:itsmechanismofactionandpotentialfortreatingdiabetesRobertoCoppari1,2,3andChristianBjørbæk4Abstract
2、Sincethediscoveryofleptinin1994,wenowhaveabetterunderstandingofthe cellularandmolecularmechanismsunderlyingitsbiologicaleffects.Inadditiontoitsestablishedanti
3、-obesityeffects,leptinexertsantidiabeticactionsthatareindependentofits regulationofbodyweightandfoodintake.Inparticular,leptincancorrectdiabetesinanimalmodelsoftype 1andtype 2diabetes.Inaddition,long-termleptinreplacementtherapyimprovesglycaemiccontrol,insulinsensitivityandplasma
4、triglyceridesinpatientswithsevereinsulinresistanceduetolipodystrophy.Theseresultshavespurredenthusiasmfortheuseofleptintherapytotreatdiabetes.Here,wereviewthecurrentunderstandingoftheglucoregulatoryfunctionsofleptin,emphasizingitscentralmechanismsofactionandlessonslearnedfromclin
5、icalstudies,anddiscusspossibletherapeuticapplicationsofleptininthetreatmentoftype 1andtype 2diabetes.Despitetheavailabilityofimprovedantidiabeticdrugs,isthoughttomediateallactionsofleptinviatheactiva-enhancedglycaemiamonitoringsystemsandeasiertionofmultipleintracellularsignalling
6、pathways(FIG. 1).patient-to-physicianaccessibility,patientswithtype 2Studiesinrodentshaveidentifiedsomeofthespecificdiabetes1,2(BOX 1)arestillatasignificantlyhigherriskneuronaltargetsthatmediatethehormonaleffectsofofdevelopingcardiovasculardiseaseandcancerthanleptinontheaforement
7、ionedparameters.Forexample,non-diabeticindividuals3,4.Theincidenceofcoronarytheactionsofleptinonbodyweightaremediatedmainly1DepartmentofInternalarterydiseaseinpatientssufferingfromtype 1diabetes5–7byGABA(γ-aminobutyricacid)-ergicneurons14(theMedicine,DivisionofHypothalamicResearc
8、h,(BOX 2)isalsoremarkablyhigh:greaterthan90%afteranatomicallocationsofwhichremainunclear),andUniversityofTexastheageof55 years8,9.IntheUnitedStates,40%ofpatientsitsroleinpubertyismediatedbyneuronswithintheSouthwesternMedicalCenter,diagnosedwithdiabetesdonotachievetheacceptedgly-v
9、entralpremammillarynucleusofthehypothala
