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1、CellMetabolismReviewHormonalRegulationofHepaticGlucoseProductioninHealthandDiseaseHuaV.Lin1andDomenicoAccili2,*1MerckResearchLaboratories,Rahway,NJ07065,USA2ColumbiaUniversityCollegeofPhysiciansandSurgeons,NewYork,NY10032,USA*Correspondence:da230@columbia.eduD
2、OI10.1016/j.cmet.2011.06.003Wereviewmechanismsthatregulateproductionofglucosebytheliver,focusingonareasofbuddingconsensus,andendeavoringtoprovideacandidassessmentoflingeringcontroversies.Wealsoattempttoreconciledatafromtracerstudiesinhumansandlargeanimalswitht
3、hegrowingcompilationofmouseknockoutsthatdisplaychangesinglucoseproduction.Aclinicalhallmarkofdiabetes,excessiveglucoseproductionremainskeytoitstreatment.Hence,weattempttointegrateemergingpathwaysintothebroadergoaltorejuvenatethestaidantidiabeticpharmacopeia.In
4、troductionthatregulationofgenetranscriptionandHGParealltoooftenHepaticglucoseproduction(HGP)isakeyphysiologicalprocessconflatedintoasingleprocess,withrecurringinterpretivethatbecomesalteredindiabeticpatients(Bogardusetal.,1984)errors.andrepresentsthemaintargeto
5、ftheantihyperglycemiceffectofTracerstudiesindogshavedefinedhormonalregulationofHGPbiguanides(Stumvolletal.,1995).Thecombinationoftracerandindetail.Asintheisolatedrodentliver,HGPisexquisitelysensitivespectroscopymethodsinhumans,selectivecatheterizationoftoglucag
6、onandinsulin.Glucagonsetsthebasaltone,butinsulinportalandhepaticveinsindogsduringtracerstudies,condi-trumpsglucagonatanyconcentration—justasitdoesinvitro.tionalknockoutsandmetabolicphenotypinginmice,andBothhormonesaffectprimarilyglycogenolysisbyreciprocalNMR-b
7、asedfluxanalysisinperfusedliverandprimaryhepato-changesofglycogensynthaseandglycogenphosphorylasecyteshasyieldedawealthofinformationonmechanismsandbymodulatingglycolysisthroughglucokinase,fructose-controllingHGP.However,theseinvestigationsappeartooccurbisphosph
8、ataseandpyruvatekinase(seebelow)(Cherrington,intangential,ifnotparallel,universes,leadingtooften-conflicting1999).Hormonalregulationofgluconeogenesishasprovendiffi-claims.Thepurposeo