2024
SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts
Goedeke L, Ma Y, Gaspar R, Nasiri A, Lee J, Zhang D, Galsgaard K, Hu X, Zhang J, Guerrera N, Li X, LaMoia T, Hubbard B, Haedersdal S, Wu X, Stack J, Dufour S, Butrico G, Kahn M, Perry R, Cline G, Young L, Shulman G. SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts. Journal Of Clinical Investigation 2024, 134: e176708. PMID: 39680452, PMCID: PMC11645152, DOI: 10.1172/jci176708.Peer-Reviewed Original ResearchConceptsSodium-glucose cotransporter type 2Heart failureKetone oxidationGas chromatography-mass spectrometryFatty acid oxidationLeft ventricular ejection fractionReduced myocardial oxidative stressVentricular ejection fractionKetone supplementationWeeks of treatmentMyocardial oxidative stressDecreased pyruvate oxidationInduce heart failurePlasma glucose levelsIn vivo effectsSGLT2i treatmentEjection fractionAssociated with improvementsAwake ratsSGLT2 inhibitionCardioprotective benefitsLiquid chromatography-tandem mass spectrometryPlasma ketonesRates of ketonizationChromatography-tandem mass spectrometry
2000
Regulation of myocardial [13C]glucose metabolism in conscious rats
McNulty P, Cline G, Whiting J, Shulman G. Regulation of myocardial [13C]glucose metabolism in conscious rats. AJP Heart And Circulatory Physiology 2000, 279: h375-h381. PMID: 10899078, DOI: 10.1152/ajpheart.2000.279.1.h375.Peer-Reviewed Original ResearchPersistent Changes in Myocardial Glucose Metabolism In Vivo During Reperfusion of a Limited-Duration Coronary Occlusion
McNulty P, Jagasia D, Cline G, Ng C, Whiting J, Garg P, Shulman G, Soufer R. Persistent Changes in Myocardial Glucose Metabolism In Vivo During Reperfusion of a Limited-Duration Coronary Occlusion. Circulation 2000, 101: 917-922. PMID: 10694532, DOI: 10.1161/01.cir.101.8.917.Peer-Reviewed Original ResearchConceptsCoronary occlusionGlucose metabolismPostischemic stunningAnterolateral left ventricleHeart glucose metabolismCoronary artery occlusionRegional glucose metabolismMyocardial glucose metabolismRegional myocardial ischemiaRegional mechanical functionRapid reperfusionReversible coronary occlusionArtery occlusionMyocardial ischemiaIntact ratsPreferential shuntingBlood flowReperfusionTracer uptakeLeft ventricleGlycogen depletionMetabolic signaturesOcclusionPersistent changesSustained changes
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
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