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
2013
Urocortin 2 autocrine/paracrine and pharmacologic effects to activate AMP-activated protein kinase in the heart
Li J, Qi D, Cheng H, Hu X, Miller EJ, Wu X, Russell KS, Mikush N, Zhang J, Xiao L, Sherwin RS, Young LH. Urocortin 2 autocrine/paracrine and pharmacologic effects to activate AMP-activated protein kinase in the heart. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 16133-16138. PMID: 24043794, PMCID: PMC3791748, DOI: 10.1073/pnas.1312775110.Peer-Reviewed Original ResearchMeSH KeywordsAcetyl-CoA CarboxylaseAMP-Activated Protein KinasesAnalysis of VarianceAnimalsAntibodies, NeutralizingCorticotropin-Releasing HormoneEnzyme ActivationImmunoblottingImmunohistochemistryMiceMyocardiumPeptide FragmentsPhosphorylationReceptors, Corticotropin-Releasing HormoneReperfusion InjurySignal TransductionUrocortinsConceptsIschemia/reperfusionIschemia/reperfusion injuryUCN2 treatmentReperfusion injuryContractile dysfunctionRegional ischemia/reperfusionAMPK activationHeart muscleIschemic AMPK activationAutocrine/paracrine pathwayCardiac contractile dysfunctionAutocrine/paracrine factorCorticotropin-releasing factor (CRF) familyIsolated heart muscleCRFR2 antagonistAcetyl-CoA carboxylase phosphorylationCardiac damageMyocardial injuryCRF receptorsPharmacologic effectsUrocortin 2ΕV1-2Activation of AMPParacrine pathwaysReperfusion