2010
Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice
Ayala JE, Consortium F, Samuel V, Morton G, Obici S, Croniger C, Shulman G, Wasserman D, McGuinness O. Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice. Disease Models & Mechanisms 2010, 3: 525-534. PMID: 20713647, PMCID: PMC2938392, DOI: 10.1242/dmm.006239.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseCatheterizationDiagnostic Techniques, EndocrineFastingGlucoseGlucose Tolerance TestHomeostasisHyperglycemiaInsulinMiceModels, AnimalPhenotype
2005
Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents
Morino K, Petersen KF, Dufour S, Befroy D, Frattini J, Shatzkes N, Neschen S, White MF, Bilz S, Sono S, Pypaert M, Shulman GI. Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. Journal Of Clinical Investigation 2005, 115: 3587-3593. PMID: 16284649, PMCID: PMC1280967, DOI: 10.1172/jci25151.Peer-Reviewed Original ResearchMeSH KeywordsBiopsyBlood GlucoseBlotting, WesternBody Mass IndexBody WeightDiabetes Mellitus, Type 2DNA, MitochondrialFamily HealthFemaleGene Expression RegulationGlucose Clamp TechniqueGlucose Tolerance TestHumansHyperinsulinismImmunoprecipitationInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceLipidsMaleMicroscopy, ElectronMicroscopy, Electron, TransmissionMitochondriaMusclesPhosphoproteinsPhosphorylationProtein Serine-Threonine KinasesReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSerineSignal TransductionTime FactorsTranscription, GeneticTriglyceridesConceptsInsulin-resistant offspringIR offspringType 2 diabetesInsulin-stimulated muscle glucose uptakeType 2 diabetic parentsIntramyocellular lipid contentHyperinsulinemic-euglycemic clampMuscle glucose uptakeIRS-1 serine phosphorylationMuscle mitochondrial densityMitochondrial densityMuscle biopsy samplesSerine kinase cascadeInsulin-stimulated Akt activationDiabetic parentsInsulin resistanceControl subjectsBiopsy samplesGlucose uptakeLipid accumulationMitochondrial dysfunctionInsulin signalingAkt activationEarly defectsMuscle
2004
Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes
Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes. New England Journal Of Medicine 2004, 350: 664-671. PMID: 14960743, PMCID: PMC2995502, DOI: 10.1056/nejmoa031314.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAdipose TissueBlood GlucoseDiabetes Mellitus, Type 2Fatty AcidsFemaleGlucoseGlucose Clamp TechniqueGlucose Tolerance TestGlycerolHumansInsulinInsulin ResistanceLipolysisMagnetic Resonance SpectroscopyMaleMitochondriaMuscle, SkeletalOxidative PhosphorylationTriglyceridesConceptsInsulin-resistant offspringType 2 diabetesIntramyocellular lipid contentInsulin-sensitive control subjectsMagnetic resonance spectroscopy studyInsulin resistanceControl subjectsProton magnetic resonance spectroscopy studyHyperinsulinemic-euglycemic clamp studiesTumor necrosis factor alphaImpaired mitochondrial activityIntrahepatic triglyceride contentDevelopment of diabetesChildren of patientsInsulin-resistant subjectsNecrosis factor alphaSensitivity of liverInsulin-stimulated ratesFatty acid metabolismMitochondrial oxidative phosphorylation activityInterleukin-6Intramyocellular lipidsPlasma concentrationsFactor alphaClamp studies
2001
Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance
Kim J, Fillmore J, Chen Y, Yu C, Moore I, Pypaert M, Lutz E, Kako Y, Velez-Carrasco W, Goldberg I, Breslow J, Shulman G. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 7522-7527. PMID: 11390966, PMCID: PMC34701, DOI: 10.1073/pnas.121164498.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseFatty Acids, NonesterifiedGlucagonGlucoseGlucose Clamp TechniqueGlucose Tolerance TestHeterozygoteInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceLeptinLipoprotein LipaseLiverMiceMice, KnockoutMice, TransgenicMuscle, SkeletalOrgan SpecificityPhosphatidylinositol 3-KinasesPhosphoproteinsSignal TransductionTriglyceridesConceptsInsulin resistanceFatty acid-derived metabolitesInsulin actionTriglyceride contentType 2 diabetes mellitusInsulin activationLipoprotein lipaseInsulin receptor substrate-1-associated phosphatidylinositolMuscle triglyceride contentSkeletal muscleTissue-specific insulin resistanceLiver triglyceride contentAdipocyte-derived hormoneHyperinsulinemic-euglycemic clampEndogenous glucose productionLiver-specific overexpressionTissue-specific overexpressionInsulin-stimulated glucose uptakeDiabetes mellitusTissue-specific increaseTransgenic miceGlucose productionFat metabolismGlucose uptakeInsulinInsulin Resistance and a Diabetes Mellitus-Like Syndrome in Mice Lacking the Protein Kinase Akt2 (PKBβ)
Cho H, Mu J, Kim J, Thorvaldsen J, Chu Q, Crenshaw E, Kaestner K, Bartolomei M, Shulman G, Birnbaum M. Insulin Resistance and a Diabetes Mellitus-Like Syndrome in Mice Lacking the Protein Kinase Akt2 (PKBβ). Science 2001, 292: 1728-1731. PMID: 11387480, DOI: 10.1126/science.292.5522.1728.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseDeoxyglucoseDiabetes Mellitus, Type 2FemaleGene TargetingGlucoseGlucose Clamp TechniqueGlucose Tolerance TestHomeostasisInsulinInsulin ResistanceIslets of LangerhansLiverMaleMiceMice, Inbred C57BLMice, TransgenicMuscle, SkeletalProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktSignal TransductionConceptsSerine-threonine protein kinase AktProtein kinase Akt2Protein kinase AktProtein kinase B.Activation of phosphatidylinositolEssential genesKinase Akt2Kinase AktAbility of insulinGlucose homeostasisNormal glucose homeostasisAkt2Critical initial stepEarly eventsSkeletal muscleHomeostasisInsulin actionMice LackingInsulin responsivenessInitial stepActivationInsulin resistancePhosphatidylinositolBlood glucoseGenesSyntaxin 4 heterozygous knockout mice develop muscle insulin resistance
Yang C, Coker K, Kim J, Mora S, Thurmond D, Davis A, Yang B, Williamson R, Shulman G, Pessin J. Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance. Journal Of Clinical Investigation 2001, 107: 1311-1318. PMID: 11375421, PMCID: PMC209300, DOI: 10.1172/jci12274.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipose Tissue, BrownAnimalsBiological TransportGlucoseGlucose Clamp TechniqueGlucose Tolerance TestGlucose Transporter Type 4GlycogenGlycolysisHeterozygoteInsulin ResistanceLiverMembrane ProteinsMiceMice, KnockoutMonosaccharide Transport ProteinsMuscle ProteinsMuscle, SkeletalQa-SNARE ProteinsConceptsHeterozygous knockout miceInsulin-stimulated glucose uptakeGlucose uptakeKnockout miceNormal insulin-stimulated glucose uptakeWhole-body glucose uptakeHyperinsulinemic-euglycemic clamp procedureInsulin-stimulated glucose metabolismInsulin-stimulated GLUT4 translocationSkeletal muscleGLUT4 vesicle traffickingImpaired glucose toleranceMuscle insulin resistanceEarly embryonic lethalitySkeletal muscle glucose transportMuscle glucose transportCritical physiological roleGlucose toleranceInsulin resistanceClamp procedureVesicle traffickingSyntaxin 4Embryonic lethalityGlucose metabolismAnimal models
2000
Increased Energy Expenditure, Decreased Adiposity, and Tissue-Specific Insulin Sensitivity in Protein-Tyrosine Phosphatase 1B-Deficient Mice
Klaman L, Boss O, Peroni O, Kim J, Martino J, Zabolotny J, Moghal N, Lubkin M, Kim Y, Sharpe A, Stricker-Krongrad A, Shulman G, Neel B, Kahn B. Increased Energy Expenditure, Decreased Adiposity, and Tissue-Specific Insulin Sensitivity in Protein-Tyrosine Phosphatase 1B-Deficient Mice. Molecular And Cellular Biology 2000, 20: 5479-5489. PMID: 10891488, PMCID: PMC85999, DOI: 10.1128/mcb.20.15.5479-5489.2000.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsBody WeightCarrier ProteinsEnergy MetabolismFemaleGlucoseGlucose Tolerance TestHomeostasisHyperinsulinismInsulin ResistanceIon ChannelsLeptinMaleMembrane ProteinsMembrane Transport ProteinsMiceMice, Inbred C57BLMice, Mutant StrainsMitochondrial ProteinsMuscle, SkeletalProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine PhosphatasesProteinsRNA, MessengerUncoupling Protein 1Uncoupling Protein 2Uncoupling Protein 3ConceptsProtein tyrosine phosphatasePTP-1BMajor protein tyrosine phosphataseProtein tyrosine phosphatase 1BSignal transduction pathwaysTargeted gene disruptionInsulin-stimulated glucose uptakeGene disruptionTransduction pathwaysFat cell massPhosphatase 1BMajor regulatorProtein mRNA expressionCell massNull miceSkeletal muscleDeficient miceGlucose uptakeBasal metabolic rateInsulin actionMetabolic ratePhosphataseFat storesDiet-induced obesityAdipocyte number
1997
Metabolic Defects in Lean Nondiabetic Offspring of NIDDM Parents: A Cross-Sectional Study
Perseghin G, Ghosh S, Gerow K, Shulman G. Metabolic Defects in Lean Nondiabetic Offspring of NIDDM Parents: A Cross-Sectional Study. Diabetes 1997, 46: 1001-1009. PMID: 9166672, DOI: 10.2337/diab.46.6.1001.Peer-Reviewed Original ResearchConceptsInsulin resistanceInsulin sensitivityControl subjectsInsulin secretionNIDDM parentsNIDDM patientsFFA metabolismFFA concentrationsAbove confounding factorsInsulin-resistant offspringFree fatty acid levelsInverse correlationLDL cholesterol levelsHealthy control subjectsNormal insulin sensitivityIntravenous glucose bolusLower insulin sensitivityPlasma FFA concentrationEuglycemic hyperinsulinemic clampCross-sectional studyFirst-degree relativesPathogenesis of NIDDMDefective insulin secretionFatty acid levelsHigh free fatty acid levels