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
2010
Knockdown of the gene encoding Drosophila tribbles homologue 3 (Trib3) improves insulin sensitivity through peroxisome proliferator-activated receptor-γ (PPAR-γ) activation in a rat model of insulin resistance
Weismann D, Erion DM, Ignatova-Todorava I, Nagai Y, Stark R, Hsiao JJ, Flannery C, Birkenfeld AL, May T, Kahn M, Zhang D, Yu XX, Murray SF, Bhanot S, Monia BP, Cline GW, Shulman GI, Samuel VT. Knockdown of the gene encoding Drosophila tribbles homologue 3 (Trib3) improves insulin sensitivity through peroxisome proliferator-activated receptor-γ (PPAR-γ) activation in a rat model of insulin resistance. Diabetologia 2010, 54: 935-944. PMID: 21190014, PMCID: PMC4061906, DOI: 10.1007/s00125-010-1984-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzhydryl CompoundsDiabetes Mellitus, Type 2Disease Models, AnimalEpoxy CompoundsGlucose Clamp TechniqueImmunoblottingInsulin ResistanceMaleOligonucleotides, AntisensePPAR gammaProtein KinasesProtein Serine-Threonine KinasesRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionConceptsTribbles homologue 3Euglycaemic hyperinsulinaemic clampWhite adipose tissueInsulin sensitivityAdipose tissueAntisense oligonucleotideInsulin-stimulated whole-body glucose uptakeWhole-body glucose uptakeConclusions/interpretationThese dataTissue-specific insulin sensitivityGlucose uptakeSkeletal muscle glucose uptakeWhite adipose tissue massPlasma HDL cholesterolRole of PPARAdipose tissue massMuscle glucose uptakeEndogenous glucose productionExpression of PPARInsulin-sensitising effectsDependent mannerViral proto-oncogeneHDL cholesterolAkt2 activityInsulin resistance