ShortArticleAMPKActivationofMuscleAutophagyPreventsFasting-InducedHypoglycemiaandMyopathyduringAgingGraphicalAbstractHighlightsdMuscleAMPKisrequiredfortheinductionofautophagyduringfastingdAMPKisrequiredforproteolysistomaintainbloodglucoseduringfastingdAlossofAMPKacceleratesaging-inducedmyopathyandmitochondrialdysfunctionAuthorsAdamL.Bujak,JustinD.Crane,...,JonathanD.Schertzer,GregoryR.SteinbergCorrespondencegsteinberg@mcmaster.caInBriefBujaketal.highlightacriticalrolefortheenergysensorAMPKinmaintainingglycemiaandmusclehomeostasis.Duringfasting,muscleAMPKinducesautophagyandmuscleproteinbreakdowntopreventhypoglycemia.Witholdage,AMPKdelaystheonsetofmusclemyopathyandmitochondrialdysfunction.Bujaketal.,2015,CellMetabolism21,883–890June2,2015ª2015ElsevierInc.http://dx.doi.org/10.1016/j.cmet.2015.05.016CellMetabolismShortArticleAMPKActivationofMuscleAutophagyPreventsFasting-InducedHypoglycemiaandMyopathyduringAgingAdamL.Bujak,1JustinD.Crane,1,2JamesS.Lally,1RebeccaJ.Ford,1SallyJ.Kang,1IrenaA.Rebalka,1AlexE.Green,1BruceE.Kemp,5ThomasJ.Hawke,3JonathanD.Schertzer,2,4andGregoryR.Steinberg1,4,*1DivisionofEndocrinologyandMetabolism,DepartmentofMedicine2DepartmentofPediatrics3DepartmentofPathologyandMolecularMedicine4DepartmentofBiochemistryandBiomedicalSciencesMcMasterUniversity,1280MainStreetWest,Hamilton,ONL8N3Z5,Canada5St.Vincent’sInstituteofMedicalResearchandDepartmentofMedicine,UniversityofMelbourne,41VictoriaParade,Fitzroy,VIC3065,Australia*Correspondence:gsteinberg@mcmaster.cahttp://dx.doi.org/10.1016/j.cmet.2015.05.016SUMMARYTheAMP-activatedproteinkinase(AMPK)activatesautophagy,butitsroleinagingandfasting-inducedmusclefunctionhasnotbeendefined.HerewereportthatfastingmicelackingskeletalmuscleAMPK(AMPK-MKO)resultsinhypoglycemiaandhyperketosis.Thisisnotduetodefectivefattyacidoxidation,butinsteadisrelatedtoablockinmuscleproteolysisthatleadstoreducedcirculatinglevelsofalanine,anessentialaminoacidrequiredforgluconeogenesis.Markersofmuscleautophagyincludingphosphorylation...