2008
Muscle-Specific IRS-1 Ser→Ala Transgenic Mice Are Protected From Fat-Induced Insulin Resistance in Skeletal Muscle
Morino K, Neschen S, Bilz S, Sono S, Tsirigotis D, Reznick RM, Moore I, Nagai Y, Samuel V, Sebastian D, White M, Philbrick W, Shulman GI. Muscle-Specific IRS-1 Ser→Ala Transgenic Mice Are Protected From Fat-Induced Insulin Resistance in Skeletal Muscle. Diabetes 2008, 57: 2644-2651. PMID: 18633112, PMCID: PMC2551673, DOI: 10.2337/db06-0454.Peer-Reviewed Original ResearchMeSH KeywordsAlanineAmino Acid SubstitutionAnimalsBlotting, WesternDietary FatsFemaleGlucose Clamp TechniqueGlucose Tolerance TestImmunoprecipitationInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceMaleMiceMice, Inbred C57BLMice, TransgenicMuscle, SkeletalPhosphorylationSerineTriglyceridesConceptsSerine phosphorylationIRS-1IRS-1-associated phosphatidylinositolSkeletal muscleInsulin-stimulated IRS-1-associated phosphatidylinositolWild-type transgenic miceFat-induced insulin resistanceInsulin receptor substrateTransgenic miceReceptor substrateInsulin signalingAkt phosphorylationPhosphorylationCellular mechanismsCritical roleGlucose uptakeHigh-fat feedingInsulin resistanceMuscle glucose uptakeInsulin actionVivoSerInsulin-stimulated muscle glucose uptakeImportant rolePhosphatidylinositol
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