2013
Limiting Cardiac Ischemic Injury by Pharmacological Augmentation of Macrophage Migration Inhibitory Factor–AMP-Activated Protein Kinase Signal Transduction
Wang J, Tong C, Yan X, Yeung E, Gandavadi S, Hare AA, Du X, Chen Y, Xiong H, Ma C, Leng L, Young LH, Jorgensen WL, Li J, Bucala R. Limiting Cardiac Ischemic Injury by Pharmacological Augmentation of Macrophage Migration Inhibitory Factor–AMP-Activated Protein Kinase Signal Transduction. Circulation 2013, 128: 225-236. PMID: 23753877, PMCID: PMC3781594, DOI: 10.1161/circulationaha.112.000862.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsAntigens, Differentiation, B-LymphocyteCardiotonic AgentsCells, CulturedGlucoseHistocompatibility Antigens Class IIIntramolecular OxidoreductasesIsoxazolesMacrophage Migration-Inhibitory FactorsMaleMiceMice, Inbred C57BLMice, KnockoutMyocardial InfarctionMyocardial IschemiaMyocytes, CardiacRecombinant ProteinsSignal TransductionConceptsMacrophage migration inhibitory factorCardiac ischemic injuryIschemic injuryProtective effectPostischemic left ventricular functionGlucose uptakeLeft coronary artery occlusionLeft ventricular functionCoronary artery occlusionIschemic tissue injuryMigration inhibitory factorMyocardial glucose uptakeAMPK activationTreatment of cardiomyocytesArtery occlusionMIF receptorVentricular functionIschemic myocardiumCellular glucose uptakeTissue injuryIschemia modelPharmacological augmentationFlow ischemiaSuch agonistsInhibitory factor
2008
Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart
Miller EJ, Li J, Leng L, McDonald C, Atsumi T, Bucala R, Young LH. Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart. Nature 2008, 451: 578-582. PMID: 18235500, DOI: 10.1038/nature06504.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsAntigens, Differentiation, B-LymphocyteCoronary Artery DiseaseEnzyme ActivationGenetic Predisposition to DiseaseGenotypeGlucoseHistocompatibility Antigens Class IIHumansHypoxiaMacrophage Migration-Inhibitory FactorsMiceMultienzyme ComplexesMyocardial IschemiaMyocardial Reperfusion InjuryMyocardiumPolymorphism, GeneticPromoter Regions, GeneticProtein Serine-Threonine KinasesRatsSignal TransductionConceptsIschemic heartMacrophage migration inhibitory factorLower MIF levelsCoronary artery diseaseIschemic heart diseaseMigration inhibitory factorPotential risk markerMIF levelsArtery diseaseRisk markersHeart diseaseIschemic stressCytokine MIFInhibitory factorGlucose uptakePotential drug targetsDiseaseHeartDrug targetsCellular stress responseAMPKMaster regulatorNew studiesPatientsAtherosclerosis
2005
AMP-Activated Protein Kinase Activates p38 Mitogen-Activated Protein Kinase by Increasing Recruitment of p38 MAPK to TAB1 in the Ischemic Heart
Li J, Miller EJ, Ninomiya-Tsuji J, Russell RR, Young LH. AMP-Activated Protein Kinase Activates p38 Mitogen-Activated Protein Kinase by Increasing Recruitment of p38 MAPK to TAB1 in the Ischemic Heart. Circulation Research 2005, 97: 872-879. PMID: 16179588, DOI: 10.1161/01.res.0000187458.77026.10.Peer-Reviewed Original ResearchMeSH KeywordsAminoimidazole CarboxamideAMP-Activated Protein KinasesAnimalsAnisomycinCell HypoxiaEnzyme ActivationGlucoseGlucose Transporter Type 4Intracellular Signaling Peptides and ProteinsMaleMAP Kinase Kinase 3MiceMice, Inbred C57BLMice, TransgenicMultienzyme ComplexesMyocardial IschemiaP38 Mitogen-Activated Protein KinasesProtein Serine-Threonine KinasesProtein TransportRatsRats, Sprague-DawleyRibonucleotidesConceptsMitogen-activated protein kinaseP38 mitogen-activated protein kinaseMAPK kinase 3P38 MAPK activationAlpha2 catalytic subunitProtein kinaseMAPK activationCatalytic subunitGlucose transportStress-signaling pathwaysAMPK activator 5Role of AMPKProtein kinase 1Direct molecular targetP38 MAPK inhibitorMouse heartsAMPK complexProtein TAB1Scaffold proteinGLUT4 translocationUpstream kinaseAMPK activationKinase 3Kinase 1MAPK inhibitor
2004
AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury
Russell RR, Li J, Coven DL, Pypaert M, Zechner C, Palmeri M, Giordano FJ, Mu J, Birnbaum MJ, Young LH. AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury. Journal Of Clinical Investigation 2004, 114: 495-503. PMID: 15314686, PMCID: PMC503766, DOI: 10.1172/jci19297.Peer-Reviewed Original ResearchConceptsLow-flow ischemiaGlucose uptakePostischemic reperfusionWT heartsLeft ventricular dPNormal fractional shorteningLV contractile functionPostischemic cardiac dysfunctionInsulin-stimulated glucose uptakeImportant protective roleLong-term inhibitionFatty acid oxidationFractional shorteningHeart failureVentricular dPCardiac consequencesCardiac dysfunctionCaspase-3 activityMyocardial ischemiaContractile functionReperfusionCardiac hypertrophyIschemiaTransgenic miceProtective roleRole 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
2001
Effect of 5-Aminoimidazole-4-Carboxamide-1-β-d-Ribofuranoside Infusion on In Vivo Glucose and Lipid Metabolism in Lean and Obese Zucker Rats
Bergeron R, Previs S, Cline G, Perret P, Russell III R, Young L, Shulman G. Effect of 5-Aminoimidazole-4-Carboxamide-1-β-d-Ribofuranoside Infusion on In Vivo Glucose and Lipid Metabolism in Lean and Obese Zucker Rats. Diabetes 2001, 50: 1076-1082. PMID: 11334411, DOI: 10.2337/diabetes.50.5.1076.Peer-Reviewed Original ResearchMeSH KeywordsAdenylate KinaseAminoimidazole CarboxamideAnimalsBlood GlucoseBody WeightFatty Acids, NonesterifiedGlucoseGlycerolInfusions, IntravenousInjections, IntravenousInsulinInsulin ResistanceLactatesMaleModels, AnimalMuscle, SkeletalObesityRatsRats, ZuckerReference ValuesRibonucleotidesTriglyceridesConceptsWhole-body glucose disposalInsulin-resistant rat modelObese ratsEndogenous glucose productionObese Zucker ratsRed gastrocnemius muscleInsulin infusion rateLean ratsGlucose disposalInsulin infusionRat modelInfusion rateGastrocnemius muscleZucker ratsLipid metabolismGlucose productionEndogenous glucose production rateGlucose transport activitySkeletal muscle glucose transport activityType 2 diabetesWhole-body carbohydrateInsulin-stimulated glucose uptakeInsulin-independent pathwaySkeletal muscle AMPKGlucose production rate
2000
Effect of hyperinsulinemia on myocardial amino acid uptake in patients with coronary artery disease
McNulty P, Jacob R, Deckelbaum L, Young L. Effect of hyperinsulinemia on myocardial amino acid uptake in patients with coronary artery disease. Metabolism 2000, 49: 1365-1369. PMID: 11079831, DOI: 10.1053/meta.2000.9510.Peer-Reviewed Original ResearchConceptsBranched-chain amino acidsIschemic heart diseaseMyocardial uptakeArterial plasmaHeart diseaseChronic ischemic heart diseaseCoronary artery diseasePlasma BCAA concentrationsEffect of hyperinsulinemiaMyocardial glucose uptakeNet myocardial uptakeEuglycemic insulin infusionsNet glutamate uptakeOxidative energy substratesPossible salutary effectsBCAA uptakeMyocardial utilizationEuglycemic hyperinsulinemiaArtery diseaseInsulin levelsBCAA concentrationsInsulin infusionAmino acid uptakeAnabolic effectsCardiovascular diseaseCellular 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
1996
Glucose metabolism distal to a critical coronary stenosis in a canine model of low-flow myocardial ischemia.
McNulty PH, Sinusas AJ, Shi CQ, Dione D, Young LH, Cline GC, Shulman GI. Glucose metabolism distal to a critical coronary stenosis in a canine model of low-flow myocardial ischemia. Journal Of Clinical Investigation 1996, 98: 62-69. PMID: 8690805, PMCID: PMC507401, DOI: 10.1172/jci118778.Peer-Reviewed Original ResearchConceptsLow-flow ischemiaCoronary stenosisIschemic myocardiumIschemic regionLow-flow myocardial ischemiaCritical coronary stenosisExogenous glucoseOxidative substrateMyocardial ischemiaIntact dogsGlucose metabolismNonischemic regionsClinical observationsCanine modelGlucose utilizationIschemiaBiochemical measurementsMyocardial regionsRate of incorporationIntracellular metabolismTricarboxylic acid cycle fluxStenosisMyocardiumGlucoseGlucose-derived pyruvate
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
Metabolic imaging: What are the challenges?
Young L, McNulty P. Metabolic imaging: What are the challenges? Journal Of Nuclear Cardiology 1994, 1: 213-217. PMID: 9420689, DOI: 10.1007/bf02984094.Commentaries, Editorials and Letters
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 ResearchConceptsAmino 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
1991
Myocardial protein turnover in patients with coronary artery disease. Effect of branched chain amino acid infusion.
Young LH, McNulty PH, Morgan C, Deckelbaum LI, Zaret BL, Barrett EJ. Myocardial protein turnover in patients with coronary artery disease. Effect of branched chain amino acid infusion. Journal Of Clinical Investigation 1991, 87: 554-560. PMID: 1991838, PMCID: PMC296343, DOI: 10.1172/jci115030.Peer-Reviewed Original ResearchConceptsBranched-chain amino acid infusionCoronary artery diseaseAmino acid infusionProtein turnoverBCAA infusionProtein synthesisArtery diseaseAcid infusionAmino acidsMyocardial protein turnoverCardiac double productCoronary blood flowPlasma insulin levelsMyocardial oxygen consumptionHuman heartProtein degradationNegative protein balanceEssential amino acidsMyocardial balanceInsulin levelsDouble productPhenylalanine balanceAnabolic effectsMyocardial uptakePostabsorptive patients
1989
Physiologic hyperinsulinemia stimulates lactate extraction by heart muscle in the conscious dog
Young L, Zaret B, Barrett E. Physiologic hyperinsulinemia stimulates lactate extraction by heart muscle in the conscious dog. Metabolism 1989, 38: 1115-1119. PMID: 2682138, DOI: 10.1016/0026-0495(89)90049-8.Peer-Reviewed Original ResearchConceptsPhysiologic hyperinsulinemiaConscious dogsFree fatty acidsArterial free fatty acid concentrationMumol/minHeart muscleArterial plasma insulinMyocardial lactate uptakeFree fatty acid concentrationsArterial lactate concentrationHyperinsulinemic-euglycemic clampMyocardial glucose uptakeHyperinsulinemia increasesEuglycemic hyperinsulinemiaNormal heart muscleEuglycemic clampFatty acidsPlasma insulinBasal measurementsBlood glucoseLactate extractionFatty acid concentrationsMyocardial uptakeLactate uptakeHyperinsulinemia
1988
Effect of Chronic Diabetes on Myocardial Fuel Metabolism and Insulin Sensitivity
Barrett E, Schwartz R, Young L, Jacob R, Zaret B. Effect of Chronic Diabetes on Myocardial Fuel Metabolism and Insulin Sensitivity. Diabetes 1988, 37: 943-948. PMID: 3290011, DOI: 10.2337/diab.37.7.943.Peer-Reviewed Original ResearchConceptsArterial free fatty acidsFree fatty acidsMyocardial balanceInsulin clampBranched-chain amino acid concentrationsEuglycemic insulin clamp techniqueGlucose uptakeInsulin-induced hypoaminoacidemiaInsulin clamp techniqueInsulin-deficient diabetesPlasma glucose concentrationFuel substrate metabolismSignificant myocardial uptakeEffect of insulinMyocardial fuel metabolismSignificant glucose uptakePhysiologic hyperinsulinemiaBasal periodChronic diabetesDiabetic animalsInsulin sensitivityAcute effectsAdditional dogsAmino acid concentrationsMyocardial uptake