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
2000
Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2
Kido Y, Burks D, Withers D, Bruning J, Kahn C, White M, Accili D. Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2. Journal Of Clinical Investigation 2000, 105: 199-205. PMID: 10642598, PMCID: PMC377430, DOI: 10.1172/jci7917.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsBlood GlucoseCell SizeDiabetes Mellitus, Type 2Disease Models, AnimalHeterozygoteHomozygoteHyperglycemiaInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsIslets of LangerhansLiverMaleMiceMice, KnockoutMuscle, SkeletalMutationOrgan SpecificityPhosphatidylinositol 3-KinasesPhosphoproteinsReceptor, InsulinConceptsBeta-cell hyperplasiaSevere insulin resistanceInsulin resistanceSkeletal muscleInsulin actionAltered beta-cell functionCompensatory beta-cell hyperplasiaMild insulin resistanceTissue-specific insulin resistanceBeta-cell functionUnderlying metabolic abnormalitiesType 2 diabetesInsulin receptorHeterozygous null mutationsDiabetic miceMetabolic abnormalitiesInsulin receptor substrateAdipose tissueRole of IRSType 2MiceHyperplasiaLiverMuscleIRS-2