2022
122-LB: Effect of Dapagliflozin on Mitochondrial Metabolism and Cardiac Function in the Failing Heart
GOEDEKE L, MA Y, ZHANG J, GUERRERA N, WU X, ZHANG D, KAHN M, ZHANG X, YOUNG L, SHULMAN G. 122-LB: Effect of Dapagliflozin on Mitochondrial Metabolism and Cardiac Function in the Failing Heart. Diabetes 2022, 71 DOI: 10.2337/db22-122-lb.Peer-Reviewed Original ResearchDAPA treatmentLV ejection fractionEjection fractionHeart failureMI ratsCardiac outputMyocardial infarctionCardiac functionLeft ventricularEffect of dapagliflozinMale Sprague-DawleyPlasma glucose concentrationMalonyl-CoA contentMitochondrial oxidationKetone availabilityΒOHB levelsVehicle treatmentPermanent ligationSGLT2 inhibitionSGLT2 inhibitorsCardioprotective effectsCoronary arteryAcetyl-CoA contentFailing HeartMitochondrial metabolism
2020
Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis
Perry RJ, Zhang D, Guerra MT, Brill AL, Goedeke L, Nasiri AR, Rabin-Court A, Wang Y, Peng L, Dufour S, Zhang Y, Zhang XM, Butrico GM, Toussaint K, Nozaki Y, Cline GW, Petersen KF, Nathanson MH, Ehrlich BE, Shulman GI. Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis. Nature 2020, 579: 279-283. PMID: 32132708, PMCID: PMC7101062, DOI: 10.1038/s41586-020-2074-6.Peer-Reviewed Original ResearchConceptsHepatic steatosisType 2Nonalcoholic fatty liver diseaseDiet-induced hepatic steatosisFatty liver diseasePlasma glucagon concentrationsHepatic adipose triglyceride lipaseHepatic acetyl-CoA contentHepatic glucose productionRatio of insulinHepatic glucose metabolismInositol triphosphate receptorAdipose triglyceride lipaseMitochondrial oxidationMitochondrial fat oxidationGlucose intoleranceLiver diseaseGlucagon concentrationsInsulin resistancePortal veinAcetyl-CoA contentHepatic lipolysisGlucagon biologyGlucose metabolismKnockout mice
2019
19-OR: Controlled-Release Mitochondrial Protonophore (CRMP) Reverses Hypertriglyceridemia and Hepatic Steatosis in Dysmetabolic Nonhuman Primates
GOEDEKE L, ROMERAL V, BUTRICO G, KAHN M, DUFOUR S, ZHANG X, CLINE G, PETERSEN K, CHNG K, SHULMAN G. 19-OR: Controlled-Release Mitochondrial Protonophore (CRMP) Reverses Hypertriglyceridemia and Hepatic Steatosis in Dysmetabolic Nonhuman Primates. Diabetes 2019, 68 DOI: 10.2337/db19-19-or.Peer-Reviewed Original ResearchControlled-release mitochondrial protonophoreSpouse/partnerCRMP treatmentInsulin resistanceDiet-induced rodent modelJanssen ResearchReversal of hypertriglyceridemiaNAFLD/NASHInflammation/fibrosisNonhuman primate modelMitochondrial protonophoreEndogenous glucose productionHepatic insulin resistanceHepatic acetyl-CoA contentAdvisory PanelMitochondrial fat oxidationMetabolic syndromeFatty liverHepatic steatosisAdverse reactionsHepatic triglyceridesAcetyl-CoA contentPrimate modelNovo Nordisk A/S.Food intake
2018
Mechanisms by Which Glucagon Acutely Stimulates Hepatic Mitochondrial Oxidation and Gluconeogenesis
PERRY R, WANG Y, BRILL A, PENG L, ZHANG D, DUFOUR S, ZHANG Y, ZHANG X, NOZAKI Y, CLINE G, EHRLICH B, PETERSEN K, SHULMAN G. Mechanisms by Which Glucagon Acutely Stimulates Hepatic Mitochondrial Oxidation and Gluconeogenesis. Diabetes 2018, 67 DOI: 10.2337/db18-146-or.Peer-Reviewed Original ResearchSpouse/partnerHigh-fat diet-induced hepatic steatosisNonalcoholic fatty liver diseaseDiet-induced hepatic steatosisGilead SciencesFatty liver diseasePlasma glucagon concentrationsType 2 diabetesHepatic acetyl-CoA contentLiver-specific knockdownIntracellular calcium signalingMitochondrial oxidationGlucose intoleranceAdipocyte triglyceride lipaseLiver diseaseWT miceGlucagon concentrationsHepatic steatosisGlucagon infusionAcetyl-CoA contentChronic increaseHepatic mitochondrial oxidationGlucagon biologyGlucagon stimulationKnockout miceMechanism by Which Dapagliflozin Induces Euglycemic Ketoacidosis in Rats
PERRY R, SONG J, WANG Y, SHULMAN G. Mechanism by Which Dapagliflozin Induces Euglycemic Ketoacidosis in Rats. Diabetes 2018, 67 DOI: 10.2337/db18-254-or.Peer-Reviewed Original ResearchSodium-glucose transport protein 2 inhibitorsHepatic glucose productionEffect of dapagliflozinEuglycemic ketoacidosisHepatic ketogenesisVolume depletionGlucose productionPlasma catecholaminesWhite adipose tissue lipolysisPlasma glucagon concentrationsExtracellular volume depletionPlasma insulin levelsAdipose tissue lipolysisPlasma insulin concentrationHepatic acetyl-CoA contentNormal Sprague-DawleyICV injectionWAT lipolysisInsulin levelsFurosemide treatmentGlucagon concentrationsAcetyl-CoA contentSaline infusionTissue lipolysisInsulin concentrations