2022
Muscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy
Riaz M, Park J, Sewanan LR, Ren Y, Schwan J, Das SK, Pomianowski PT, Huang Y, Ellis MW, Luo J, Liu J, Song L, Chen IP, Qiu C, Yazawa M, Tellides G, Hwa J, Young LH, Yang L, Marboe CC, Jacoby DL, Campbell SG, Qyang Y. Muscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy. Circulation 2022, 145: 1238-1253. PMID: 35384713, PMCID: PMC9109819, DOI: 10.1161/circulationaha.121.056265.Peer-Reviewed Original ResearchConceptsHypertrophic cardiomyopathySarcomeric mutationsFamilial hypertrophic cardiomyopathySudden cardiac deathCardiac myosin heavy chainMechanism-based treatmentsDevelopment of hypertrophyActivated T cellsCalcineurin-nuclear factorForce productionPhenotypic expressionPluripotent stem cell-derived cardiomyocytesStem cell-derived cardiomyocytesHeart failureCardiac deathVentricular hypertrophyCell-derived cardiomyocytesCardiac contractilityPharmacological interventionsT cellsCardiac diseaseCardiac hypertrophyPatient-specific induced pluripotent stem cellsPharmacological meansTwitch relaxation
2004
Role of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4 translocation in heart muscle
Li J, Hu X, Selvakumar P, Russell RR, Cushman SW, Holman GD, Young LH. Role of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4 translocation in heart muscle. AJP Endocrinology And Metabolism 2004, 287: e834-e841. PMID: 15265762, DOI: 10.1152/ajpendo.00234.2004.Peer-Reviewed Original ResearchMeSH KeywordsAminoimidazole CarboxamideAMP-Activated Protein KinasesAnimalsBiological TransportEnzyme ActivationGlucoseGlucose Transporter Type 4Hypoglycemic AgentsIn Vitro TechniquesMaleMonosaccharide Transport ProteinsMultienzyme ComplexesMuscle ProteinsNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIPapillary MusclesProtein Serine-Threonine KinasesProtein TransportRatsRats, Sprague-DawleyRibonucleotidesConceptsGLUT4 translocationAMPK stimulationGlucose transportAMPK catalytic subunitGlucose uptakeCell surfaceGlucose transporter GLUT4Serine-threonine kinaseEndothelial NO synthasePotential downstream mediatorsVesicular traffickingCatalytic subunitProtein kinaseAICAR treatmentCellular metabolismNitric oxide pathwayAMPKDownstream mediatorTranslocationEssential roleHeart muscleOxide pathwayCyclase pathwayPathwayAICAR
2003
Physiological role of AMP-activated protein kinase in the heart: graded activation during exercise
Coven DL, Hu X, Cong L, Bergeron R, Shulman GI, Hardie DG, Young LH. Physiological role of AMP-activated protein kinase in the heart: graded activation during exercise. AJP Endocrinology And Metabolism 2003, 285: e629-e636. PMID: 12759223, DOI: 10.1152/ajpendo.00171.2003.Peer-Reviewed Original ResearchConceptsAMPK activityProtein kinasePhysiological roleTotal AMPK activityAlpha2 catalytic subunitCellular metabolic processesAlpha catalytic subunitCardiac AMPK activityAMPK effectsAMPK activationMetabolic processesAMPKAkt phosphorylationKinasePhosphorylationSkeletal muscleSubunitsSubstrate metabolismActivationActivity increasesLesser extentMyocardial substrate metabolismMin of treadmillHigh-intensity exerciseActivity
2002
AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation
Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ, Shulman GI. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 15983-15987. PMID: 12444247, PMCID: PMC138551, DOI: 10.1073/pnas.252625599.Peer-Reviewed Original ResearchMeSH KeywordsAdenine NucleotidesAdenylate KinaseAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium-Calmodulin-Dependent Protein Kinase Type 4Calcium-Calmodulin-Dependent Protein KinasesEnergy MetabolismEnzyme InductionGene Expression RegulationGenes, DominantGuanidinesMiceMice, TransgenicMitochondria, MuscleMuscle ProteinsMuscle, SkeletalPhosphocreatinePropionatesTranscription FactorsConceptsMitochondrial biogenesisPeroxisome proliferator-activated receptor-gamma coactivator-1alphaDominant negative mutantProliferator-activated receptor-gamma coactivator-1alphaRole of AMPReceptor-gamma coactivator-1alphaGamma coactivator-1alphaProtein kinaseAMPK inactivationEnergy deprivationBiogenesisAMPK activityDN-AMPKMuscle AMPKCritical adaptationKinase IVCritical regulatorAMP kinaseCoactivator-1alphaMitochondrial contentAMPKFuel sensorEnergy statusKinase
2000
Cellular and molecular regulation of cardiac glucose transport
Young L, Coven D, Russell R. Cellular and molecular regulation of cardiac glucose transport. Journal Of Nuclear Cardiology 2000, 7: 267-276. PMID: 10888399, DOI: 10.1016/s1071-3581(00)70016-x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
1999
Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR
Russell R, Bergeron R, Shulman G, Young L. Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR. American Journal Of Physiology 1999, 277: h643-h649. PMID: 10444490, DOI: 10.1152/ajpheart.1999.277.2.h643.Peer-Reviewed Original ResearchMeSH KeywordsAminoimidazole CarboxamideAMP-Activated Protein KinasesAnimalsBiological TransportEnzyme ActivationGlucoseGlucose Transporter Type 4In Vitro TechniquesMaleMonosaccharide Transport ProteinsMultienzyme ComplexesMuscle ProteinsMyocardiumProtein Serine-Threonine KinasesRatsRats, Sprague-DawleyRibonucleotidesSarcolemmaConceptsAMPK activationGLUT-4 translocationGLUT-4Glucose uptakeProtein kinase activityActivator of AMPKActivation of AMPKInsulin-stimulated increasePI3K-independent pathwayInsulin-stimulated glucose uptakePI3K inhibitorsKinase activityAICARDeoxyglucose uptakeAMPKTranslocationIschemia-induced translocationK inhibitorsAdenine 9Myocyte sarcolemmaPathwayImmunofluorescence studiesMuscle glucose uptakeActivationCardiac myocytesRegulation of myocardial glucose uptake and transport during ischemia and energetic stress
Young L, Russell R, Yin R, Caplan M, Ren J, Bergeron R, Shulman G, Sinusas A. Regulation of myocardial glucose uptake and transport during ischemia and energetic stress. The American Journal Of Cardiology 1999, 83: 25-30. PMID: 10750583, DOI: 10.1016/s0002-9149(99)00253-2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsEnergetic stressEnergy-generating metabolic pathwaysMonophosphate-activated protein kinaseGlucose uptakeGlucose transport proteinProtein kinaseTransporter translocationTransport proteinsMolecular mechanismsMetabolic pathwaysCardiac glucose uptakeGlucose transporterCellular mechanismsGlucose transportFuel gaugeKinaseTranslocationGlucose entryModerate regional ischemiaSubsequent metabolismGlucose utilization increasesImportant roleUptakeGLUT4Stress
1998
Additive Effects of Hyperinsulinemia and Ischemia on Myocardial GLUT1 and GLUT4 Translocation In Vivo
Russell R, Yin R, Caplan M, Hu X, Ren J, Shulman G, Sinusas A, Young L. Additive Effects of Hyperinsulinemia and Ischemia on Myocardial GLUT1 and GLUT4 Translocation In Vivo. Circulation 1998, 98: 2180-2186. PMID: 9815873, DOI: 10.1161/01.cir.98.20.2180.Peer-Reviewed Original Research
1997
Low-flow ischemia leads to translocation of canine heart GLUT-4 and GLUT-1 glucose transporters to the sarcolemma in vivo.
Young L, Renfu Y, Russell R, Hu X, Caplan M, Ren J, Shulman G, Sinusas A. Low-flow ischemia leads to translocation of canine heart GLUT-4 and GLUT-1 glucose transporters to the sarcolemma in vivo. Circulation 1997, 95: 415-22. PMID: 9008459, DOI: 10.1161/01.cir.95.2.415.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological TransportDogsFluorescent Antibody TechniqueGlucose Transporter Type 1Glucose Transporter Type 4HeartIntracellular MembranesMonosaccharide Transport ProteinsMuscle ProteinsMyocardial IschemiaMyocardiumRegional Blood FlowSarcolemmaSubcellular FractionsTissue Distribution
1996
IGF-I stimulation of muscle protein synthesis in the awake rat: permissive role of insulin and amino acids
Jacob R, Hu X, Niederstock D, Hasan S, McNulty PH, Sherwin RS, Young LH. IGF-I stimulation of muscle protein synthesis in the awake rat: permissive role of insulin and amino acids. American Journal Of Physiology 1996, 270: e60-e66. PMID: 8772474, DOI: 10.1152/ajpendo.1996.270.1.e60.Peer-Reviewed Original ResearchConceptsMuscle protein synthesisInsulin replacementPlasma insulinAwake ratsInsulin-like growth factor ICapacity of IGFIGF-I infusionInfusion of IGFAction of IGFSaline control valuesGrowth factor IIGF-I stimulationProtein synthesisIntravenous infusionPlasma concentrationsInsulin concentrationsAmino acid concentrationsIGFPermissive roleInfusionFactor IControl valuesInsulinRatsAmino acids
1995
Hyperinsulinemia inhibits myocardial protein degradation in patients with cardiovascular disease and insulin resistance.
McNulty P, Louard R, Deckelbaum L, Zaret B, Young L. Hyperinsulinemia inhibits myocardial protein degradation in patients with cardiovascular disease and insulin resistance. Circulation 1995, 92: 2151-6. PMID: 7554195, DOI: 10.1161/01.cir.92.8.2151.Peer-Reviewed Original ResearchConceptsMyocardial protein degradationInsulin infusionCardiovascular diseaseMyocardial protein synthesisInsulin resistancePhenylalanine balanceMyocardial hypertrophyWhole-body glucose metabolismCoronary artery diseaseIschemic heart diseasePlasma insulin concentrationNet phenylalanine balanceWhole-body carbohydrate metabolismEffect of insulinMyocardial protein metabolismArtery diseaseAcute hyperinsulinemiaProtein synthesisHeart diseaseInsulin concentrationsPlasma concentrationsAntiproteolytic actionHyperinsulinemiaGlucose metabolismConstant infusion
1994
Effect of insulin on rat heart and skeletal muscle phenylalanyl-tRNA labeling and protein synthesis in vivo
Young LH, Stirewalt W, McNulty PH, Revkin JH, Barrett EJ. Effect of insulin on rat heart and skeletal muscle phenylalanyl-tRNA labeling and protein synthesis in vivo. American Journal Of Physiology 1994, 267: e337-e342. PMID: 8074214, DOI: 10.1152/ajpendo.1994.267.2.e337.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsInsulinMaleMuscle ProteinsMusclesMyocardiumPhenylalanineRatsRats, Sprague-DawleyRNA, TransferConceptsMuscle protein synthesisAcid-soluble poolFemoral venous plasmaSkeletal muscleSkeletal muscle protein synthesisEffect of insulinMuscle protein hydrolysateProtein synthesisContinuous infusionVenous plasmaHyperinsulinemic clampSaline infusionAnesthetized ratsArterial plasmaRat heartInsulin effectInsulinHormonal regulationHeartInfusionMuscleSpecific activityMinVivo measurementsLabeling
1993
Response of rat heart and skeletal muscle protein in vivo to insulin and amino acid infusion
McNulty PH, Young LH, Barrett EJ. Response of rat heart and skeletal muscle protein in vivo to insulin and amino acid infusion. American Journal Of Physiology 1993, 264: e958-e965. PMID: 8333520, DOI: 10.1152/ajpendo.1993.264.6.e958.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGlucoseInsulinLeucineMaleMuscle ProteinsMusclesMyocardiumOsmolar ConcentrationPhenylalanineRatsRats, Sprague-DawleyConceptsAmino acid infusionMuscle protein synthesisContinuous infusionAcid infusionNet muscle protein synthesisSaline-treated ratsSkeletal muscle protein synthesisInfusion of insulinPlasma specific activitySkeletal muscle proteinsProtein synthesisAmino acid solutionMature ratsInfusionRat heartInsulinBolusTracer infusionHeart muscleSkeletal muscleTracer infusion methodRatsPhysiological concentrationsAmino acids
1992
Physiological hyperinsulinemia inhibits myocardial protein degradation in vivo in the canine heart.
Young LH, Dahl DM, Rauner D, Barrett EJ. Physiological hyperinsulinemia inhibits myocardial protein degradation in vivo in the canine heart. Circulation Research 1992, 71: 393-400. PMID: 1628395, DOI: 10.1161/01.res.71.2.393.Peer-Reviewed Original ResearchConceptsMyocardial protein degradationProtein degradationProtein synthesisMyocardial protein turnoverAmino acid replacementsAcid replacementsProtein turnoverEssential amino acidsAmino acidsPhenylalanine balanceAmino acid concentrationsNet myocardial releaseSpecific activityPhenylalanineVivoDegradationAnimalsBasal rateIsotopic steady statePhysiological hyperinsulinemiaTurnover
1987
An isotopic method for measurement of muscle protein synthesis and degradation in vivo
Barrett EJ, Revkin JH, Young LH, Zaret BL, Jacob R, Gelfand RA. An isotopic method for measurement of muscle protein synthesis and degradation in vivo. Biochemical Journal 1987, 245: 223-228. PMID: 3663148, PMCID: PMC1148103, DOI: 10.1042/bj2450223.Peer-Reviewed Original ResearchMeSH KeywordsAmino AcidsAnimalsArteriesDogsFemaleFemoral VeinLeucineMaleMuscle ProteinsPhenylalanineTritiumConceptsNet amino acid releaseFemoral venous plasmaTissue blood flowAmino acid releaseMuscle protein synthesisHindlimb flowTissue protein degradationSpecific radioactivityContinuous infusionUptake of leucineMuscle bedArterial circulationClinical studiesPlasma concentrationsDog hindlimbBlood flowProtein synthesisAcid releaseHindlimbProtein turnoverTissue proteinsPhenylalanine incorporationRemoval of tracerMuscle tissueDogs