2014
A Role for Mitochondrial Phosphoenolpyruvate Carboxykinase (PEPCK-M) in the Regulation of Hepatic Gluconeogenesis*
Stark R, Guebre-Egziabher F, Zhao X, Feriod C, Dong J, Alves TC, Ioja S, Pongratz RL, Bhanot S, Roden M, Cline GW, Shulman GI, Kibbey RG. A Role for Mitochondrial Phosphoenolpyruvate Carboxykinase (PEPCK-M) in the Regulation of Hepatic Gluconeogenesis*. Journal Of Biological Chemistry 2014, 289: 7257-7263. PMID: 24497630, PMCID: PMC3953244, DOI: 10.1074/jbc.c113.544759.Peer-Reviewed Original ResearchMeSH KeywordsAnimal FeedAnimalsBlood GlucoseFood DeprivationGene Expression Regulation, EnzymologicGene SilencingGluconeogenesisGlycerolGlycogenGuanosine TriphosphateHepatocytesHomeostasisInsulinIntracellular Signaling Peptides and ProteinsIsoenzymesLactic AcidLiverMaleMitochondriaOligonucleotides, AntisenseOxygenOxygen ConsumptionPhosphoenolpyruvate Carboxykinase (GTP)RatsRats, Sprague-Dawley
2010
Resistance to High-Fat Diet-Induced Obesity and Insulin Resistance in Mice with Very Long-Chain Acyl-CoA Dehydrogenase Deficiency
Zhang D, Christianson J, Liu ZX, Tian L, Choi CS, Neschen S, Dong J, Wood PA, Shulman GI. Resistance to High-Fat Diet-Induced Obesity and Insulin Resistance in Mice with Very Long-Chain Acyl-CoA Dehydrogenase Deficiency. Cell Metabolism 2010, 11: 402-411. PMID: 20444420, PMCID: PMC3146169, DOI: 10.1016/j.cmet.2010.03.012.Peer-Reviewed Original ResearchConceptsMitochondrial fatty acid oxidationFatty acid oxidationMitochondrial fatty acid oxidation enzymesProtein kinase CthetaLong-chain acyl-CoA dehydrogenaseAcid oxidationFatty acid oxidation enzymesAcyl-CoA dehydrogenaseDiet-induced obesityMuscle insulin resistanceLong-Chain AcylInsulin resistanceCellular metabolismOxidation enzymesDiacylglycerol contentHigh-fat diet-induced obesityFat Diet-Induced ObesityType 2 diabetesImportant energy sourceCoA dehydrogenase deficiencyChronic activationInsulin sensitivity
2009
The Role of Peroxisome Proliferator-Activated Receptor γ Coactivator-1 β in the Pathogenesis of Fructose-Induced Insulin Resistance
Nagai Y, Yonemitsu S, Erion DM, Iwasaki T, Stark R, Weismann D, Dong J, Zhang D, Jurczak MJ, Löffler MG, Cresswell J, Yu XX, Murray SF, Bhanot S, Monia BP, Bogan JS, Samuel V, Shulman GI. The Role of Peroxisome Proliferator-Activated Receptor γ Coactivator-1 β in the Pathogenesis of Fructose-Induced Insulin Resistance. Cell Metabolism 2009, 9: 252-264. PMID: 19254570, PMCID: PMC3131094, DOI: 10.1016/j.cmet.2009.01.011.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsDietFructoseGene ExpressionHepatocytesHumansInsulin ResistanceLiverMaleMiceOligonucleotides, AntisensePeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaRatsRats, Sprague-DawleyRNA-Binding ProteinsSterol Regulatory Element Binding Protein 1Transcription FactorsConceptsInsulin resistancePeroxisome proliferator-activated receptor gamma coactivator 1 betaInsulin-stimulated whole-body glucose disposalWhole-body glucose disposalPGC-1betaTreatment of NAFLDFructose-Induced Insulin ResistanceHepatic insulin resistanceWhite adipose tissueDe novo lipogenesisSREBP-1Downstream lipogenic genesReceptor γ coactivatorGlucose disposalInsulin-stimulated statesHepatic lipogenesisNovo lipogenesisTherapeutic targetAdipose tissuePeroxisome proliferatorLipogenic genesΓ coactivatorGlucose uptakePathogenesisMetabolic phenotype
2007
Mitochondrial dysfunction due to long-chain Acyl-CoA dehydrogenase deficiency causes hepatic steatosis and hepatic insulin resistance
Zhang D, Liu ZX, Choi CS, Tian L, Kibbey R, Dong J, Cline GW, Wood PA, Shulman GI. Mitochondrial dysfunction due to long-chain Acyl-CoA dehydrogenase deficiency causes hepatic steatosis and hepatic insulin resistance. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 17075-17080. PMID: 17940018, PMCID: PMC2040460, DOI: 10.1073/pnas.0707060104.Peer-Reviewed Original ResearchMeSH KeywordsAcyl Coenzyme AAcyl-CoA Dehydrogenase, Long-ChainAnimalsCalorimetryCarbon IsotopesDiglyceridesEnergy MetabolismFatty LiverGene Expression RegulationGlucoseHomeostasisInsulinInsulin ResistanceLiverMiceMitochondriaMuscle, SkeletalOxidation-ReductionProtein Kinase C-epsilonSignal TransductionTriglyceridesConceptsLong-chain acyl-CoA dehydrogenaseHepatic insulin resistanceInsulin stimulationMitochondrial functionInsulin resistanceMitochondrial fatty acid oxidation capacityMitochondrial fatty acid oxidationAcyl-CoA dehydrogenaseHepatic steatosisFatty acid oxidation capacityAkt2 activationDe novo synthesisFatty acid oxidationPKCepsilon activationKey enzymeHyperinsulinemic-euglycemic clampLong-chain acyl-CoA dehydrogenase deficiencyType 2 diabetesPrimary defectMitochondrial dysfunctionHepatic glucose productionAcyl-CoA dehydrogenase deficiencyPKCepsilon activityNovo synthesisDiacylglycerol accumulation
2005
Hormone-sensitive lipase knockout mice have increased hepatic insulin sensitivity and are protected from short-term diet-induced insulin resistance in skeletal muscle and heart
Park SY, Kim HJ, Wang S, Higashimori T, Dong J, Kim YJ, Cline G, Li H, Prentki M, Shulman GI, Mitchell GA, Kim JK. Hormone-sensitive lipase knockout mice have increased hepatic insulin sensitivity and are protected from short-term diet-induced insulin resistance in skeletal muscle and heart. AJP Endocrinology And Metabolism 2005, 289: e30-e39. PMID: 15701680, DOI: 10.1152/ajpendo.00251.2004.Peer-Reviewed Original ResearchConceptsHSL-KO miceHormone-sensitive lipaseDiet-induced insulin resistanceHSL-deficient miceHigh-fat feedingInsulin resistanceSkeletal muscleGlucose metabolismInsulin actionTissue-specific insulin actionWhole-body fat massGlucose uptakeDiabetic heart failureDiet-induced obesityNormal chow dietBody fat massGroups of miceHyperinsulinemic-euglycemic clampType 2 diabetesFatty acyl-CoA levelsHepatic insulin actionHepatic insulin sensitivityWild-type miceLiver glucose metabolismCardiac glucose uptake
2001
Glucose toxicity and the development of diabetes in mice with muscle-specific inactivation of GLUT4
Kim J, Zisman A, Fillmore J, Peroni O, Kotani K, Perret P, Zong H, Dong J, Kahn C, Kahn B, Shulman G. Glucose toxicity and the development of diabetes in mice with muscle-specific inactivation of GLUT4. Journal Of Clinical Investigation 2001, 108: 153-160. PMID: 11435467, PMCID: PMC353719, DOI: 10.1172/jci10294.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAge of OnsetAnimalsDepression, ChemicalDiabetes Mellitus, Type 2Disease Models, AnimalGlucoseGlucose Transporter Type 4HyperglycemiaInsulinInsulin Infusion SystemsInsulin ResistanceKidney TubulesLiverMaleMiceMice, KnockoutMonosaccharide Transport ProteinsMuscle ProteinsMuscle, SkeletalPhlorhizinPrediabetic StateProtein TransportConceptsDevelopment of diabetesMuscle glucose uptakeKO miceHepatic glucose productionInsulin-stimulated glucose uptakeGlucose toxicityMuscle-specific inactivationGlucose uptakeAdipose tissueInsulin-stimulated muscle glucose uptakeGlucose productionWhole-body glucose uptakeSkeletal muscle glucose uptakeAdipose tissue glucose uptakeSuppress hepatic glucose productionTissue glucose uptakeHyperinsulinemic-euglycemic clampMuscle glucose transportInsulin resistanceTransgenic miceDiabetes phenotypeInsulin actionPhloridzin treatmentInsulin's abilityDiabetes