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
2001
Insulin/IGF-1 and TNF-α stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways
Rui L, Aguirre V, Kim J, Shulman G, Lee A, Corbould A, Dunaif A, White M. Insulin/IGF-1 and TNF-α stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways. Journal Of Clinical Investigation 2001, 107: 181-189. PMID: 11160134, PMCID: PMC199174, DOI: 10.1172/jci10934.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnisomycinCHO CellsCricetinaeInsulinInsulin AntagonistsInsulin ResistanceInsulin-Like Growth Factor IMAP Kinase Kinase 1Mitogen-Activated Protein Kinase KinasesPhosphatidylinositol 3-KinasesPhosphorylationProtein Serine-Threonine KinasesReceptor, InsulinSerineSignal TransductionTumor Necrosis Factor-alphaTyrosineConceptsPhosphorylation of Ser307IRS-1Serine/threonine phosphorylationTNF-alpha-stimulated phosphorylationInsulin-stimulated tyrosine phosphorylationRelevant phosphorylation sitesDistinct kinase pathwaysInsulin/IGFInsulin-stimulated phosphorylationThreonine phosphorylationStimulates PhosphorylationPhosphorylation sitesJun kinaseTyrosine phosphorylationKinase pathwaySer307PhosphorylationCultured cellsDistinct pathwaysHeterologous inhibitionPolyclonal antibodiesPreadipocytesPathwayAdipocytesCells