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
2019
SGLT2 inhibition slows tumor growth in mice by reversing hyperinsulinemia
Nasiri AR, Rodrigues MR, Li Z, Leitner BP, Perry RJ. SGLT2 inhibition slows tumor growth in mice by reversing hyperinsulinemia. Cancer & Metabolism 2019, 7: 10. PMID: 31867105, PMCID: PMC6907191, DOI: 10.1186/s40170-019-0203-1.Peer-Reviewed Original ResearchControlled-release mitochondrial protonophoreInsulin-lowering agentsTumor growthSodium-glucose cotransporter 2 inhibitorsObesity-cancer connectionSustained weight lossCotransporter 2 inhibitorsObesity-associated cancersSubcutaneous insulin infusionInsulin-lowering effectTumor glucose uptakeBreast tumor growthMultiple comparisonsMultiple tumor typesSGLT2 inhibitionSGLT2 inhibitorsObese miceInsulin infusionColon cancer progressionTherapeutic approachesMouse modelBonferroni multiple comparisonsGlucose metabolismColon cancerHyperinsulinemia