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《Inhibition of Glycogen-synthase Kinase 3 StimulatesGlycogen Synthase and Glucose Transport byDistinct Mechanisms in 3T3-L1 Adipocytes糖原合成酶激酶3刺激的抑制作用 糖原合成酶与葡萄糖转运 3T3-L1脂肪细胞的不同机制》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、THEJOURNALOFBIOLOGICALCHEMISTRYVol.275,No.21,IssueofMay26,pp.15765±15772,2000©2000byTheAmericanSocietyforBiochemistryandMolecularBiology,Inc.PrintedinU.S.A.InhibitionofGlycogen-synthaseKinase3StimulatesGlycogenSynthaseandGlucoseTransportbyDistinctMechanismsin3T3-L1Adipocytes*Receivedforpubli
2、cation,December15,1999,andinrevisedform,March15,2000Published,JBCPapersinPress,March20,2000,DOI10.1074/jbc.M910002199StephenJ.OrenÄa,AnthonyJ.Torchia,andRobertS.Garofalo³FromPfizer,Inc.,CentralResearchDivision,Groton,Connecticut06340-8002Theroleofglycogen-synthasekinase3(GSK3)inin-B(PKB/Akt)
3、,p70S6kinase,andproteinkinaseCz(1).Onesulin-stimulatedglucosetransportandglycogensyn-targetofPKBistheSer/Thrkinase,glycogen-synthasekinasethaseactivationwasinvestigatedin3T3-L1adipocytes.3(GSK3)(2,3).TwoisoformsofGSK3,aandb,arebroadlyGSK3proteinwasclearlypresentinadipocytesandwasexpressedand
4、playmultipleregulatoryrolesindevelopmentfoundtobemoreabundantthaninmuscleandlivercellandmetabolism(4).GSK3isconstitutivelyactiveincellsandislines.TheselectiveGSK3inhibitor,LiCl,stimulatedglu-transientlyinhibitedfollowinginsulintreatment(3).Inactiva-cosetransportandglycogensynthaseactivity(20
5、andtionofGSK3byinsulinrequiresPI3-kinaseandappearstobe65%,respectively,ofthemaximal(1mM)insulinre-mediatedbyPKBphosphorylationofGSK3onSer-21(a)orDownloadedfromsponse)andpotentiatedtheresponsestoasubmaximalSer-9(b)(3).GSK3playsanimportantroleintheregulationofconcentration(1nM)ofinsulin.LiCl-a
6、ndinsulin-stimu-glycogensynthesisviainhibitoryphosphorylationofglycogenlatedglucosetransportwereabolishedbythephos-synthase.Indeed,overexpressionofGSK3bleadstoinhibitionphatidylinositol3-kinase(PI3-kinase)inhibitor,wort-ofbasalandinsulin-stimulatedglycogensynthaseactivity(6,mannin;however,Li
7、Clstimulationofglycogensynthase7).Insulinstimulationofglycogensynthesisisimpairedinwasnot.Incontrasttotherapidstimulationofglucosemusclefrompatientswithtype2diabetes(8,9).Althoughthehttp://www.jbc.org/transportbyinsulin,transportstimulatedbyLiClin-
