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
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 accumulationn-3 Fatty Acids Preserve Insulin Sensitivity In Vivo in a Peroxisome Proliferator–Activated Receptor-α–Dependent Manner
Neschen S, Morino K, Dong J, Wang-Fischer Y, Cline GW, Romanelli AJ, Rossbacher J, Moore IK, Regittnig W, Munoz DS, Kim JH, Shulman GI. n-3 Fatty Acids Preserve Insulin Sensitivity In Vivo in a Peroxisome Proliferator–Activated Receptor-α–Dependent Manner. Diabetes 2007, 56: 1034-1041. PMID: 17251275, DOI: 10.2337/db06-1206.Peer-Reviewed Original ResearchConceptsPPAR alpha-null miceHepatic insulin resistanceHigh-fat diet-induced hepatic insulin resistanceDiacylglycerol-dependent mannerInsulin resistanceWild-type miceFish oil dietOil dietPEPCK gene expressionNull miceDiet-induced hepatic insulin resistanceInsulin sensitivityPPAR-alpha nullSafflower oilFatty acidsGene expressionIsocaloric high-fat dietHigh-fat diet-induced insulin resistanceDiet-induced insulin resistancePeroxisome proliferator-activated receptorLipid abundanceFish oil replacementFish oilHigh-fat dietInsulin-mediated suppression
2005
Adipocyte-Specific Overexpression of FOXC2 Prevents Diet-Induced Increases in Intramuscular Fatty Acyl CoA and Insulin Resistance
Kim JK, Kim HJ, Park SY, Cederberg A, Westergren R, Nilsson D, Higashimori T, Cho YR, Liu ZX, Dong J, Cline GW, Enerback S, Shulman GI. Adipocyte-Specific Overexpression of FOXC2 Prevents Diet-Induced Increases in Intramuscular Fatty Acyl CoA and Insulin Resistance. Diabetes 2005, 54: 1657-1663. PMID: 15919786, DOI: 10.2337/diabetes.54.6.1657.Peer-Reviewed Original ResearchConceptsWild-type miceInsulin resistanceType 2 diabetesAdipocyte-specific overexpressionHigh-fat feedingTg miceGlucose metabolismTransgenic miceDiet-induced hepatic insulin resistanceChronic high-fat feedingTissue-specific insulin actionWhole-body fat massWhole-body glucose metabolismDiet-induced insulin resistanceIntracellular fat contentDiet-induced obesityHigh-fat dietInsulin-mediated suppressionFatty acyl-CoA levelsHepatic insulin resistanceNovel therapeutic targetHepatic glucose productionAcyl-CoA levelsIntramuscular accumulationGlucose intoleranceHormone-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
2004
Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle
Kim JK, Gimeno RE, Higashimori T, Kim HJ, Choi H, Punreddy S, Mozell RL, Tan G, Stricker-Krongrad A, Hirsch DJ, Fillmore JJ, Liu ZX, Dong J, Cline G, Stahl A, Lodish HF, Shulman GI. Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle. Journal Of Clinical Investigation 2004, 113: 756-763. PMID: 14991074, PMCID: PMC351314, DOI: 10.1172/jci18917.Peer-Reviewed Original ResearchMeSH KeywordsAdiponectinAdipose TissueAnimalsBlood GlucoseCarrier ProteinsDiabetes Mellitus, Type 2Fatty Acid Transport ProteinsFatty AcidsFemaleGene DeletionGene Expression RegulationGlucoseInsulinInsulin ResistanceIntercellular Signaling Peptides and ProteinsMaleMembrane Transport ProteinsMiceMice, KnockoutModels, GeneticMuscle, SkeletalPatch-Clamp TechniquesPhenotypeProteinsSignal TransductionConceptsFatty acid transport protein 1Fatty acid metabolitesInsulin resistanceType 2 diabetesWhole-body adiposityKO miceAcid metabolitesSkeletal muscleChronic high-fat feedingAcute lipid infusionRegular chow dietHigh-fat feedingNovel therapeutic targetFatty acid uptakeIntramuscular accumulationLipid infusionChow dietInsulin sensitivityGlucose homeostasisTherapeutic targetInsulin actionAcid uptakeProtein 1Tissue expressionMice
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