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
2017
Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms
Ferrandino G, Kaspari RR, Spadaro O, Reyna-Neyra A, Perry RJ, Cardone R, Kibbey RG, Shulman GI, Dixit VD, Carrasco N. Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e9172-e9180. PMID: 29073114, PMCID: PMC5664516, DOI: 10.1073/pnas.1707797114.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseDe novo lipogenesisAdipose tissue lipolysisHepatic insulin resistanceThyroid hormonesHypothyroid miceImpaired suppressionInsulin resistanceTissue lipolysisInsulin secretionHigh thyroid-stimulating hormone levelsRegulation of THThyroid-stimulating hormone levelsLipid utilizationFatty liver diseaseSerum glucose levelsEndogenous glucose productionLow thyroid hormoneFatty acidsHepatic lipid utilizationLiver diseaseSevere hypothyroidismHormone levelsProfound suppressionGlucose levels
2015
Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats
Perry RJ, Zhang D, Zhang XM, Boyer JL, Shulman GI. Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats. Science 2015, 347: 1253-1256. PMID: 25721504, PMCID: PMC4495920, DOI: 10.1126/science.aaa0672.Peer-Reviewed Original ResearchMeSH Keywords2,4-DinitrophenolAnimalsBlood GlucoseDelayed-Action PreparationsDiabetes Mellitus, Type 2Glucose Tolerance TestInsulin ResistanceLipid MetabolismLiver CirrhosisMaleMiceMitochondria, LiverMuscle, SkeletalNon-alcoholic Fatty Liver DiseaseOxidation-ReductionProton IonophoresRandom AllocationRatsRats, ZuckerConceptsNonalcoholic fatty liver diseaseNonalcoholic steatohepatitisInsulin resistanceRat modelControlled-release oral formulationsPlasma transaminase concentrationsFatty liver diseaseType 2 diabetesMitochondrial uncouplingProtein-synthetic functionChronic treatmentLiver diseaseMetabolic syndromeTransaminase concentrationsHepatic steatosisLiver fibrosisEffective therapyPreclinical modelsOral formulationSystemic toxicityClinical useRelated epidemicsBeneficial effectsSynthetic functionMitochondrial protonophore