2003
Molecular Mechanisms of Insulin Resistance in IRS-2-Deficient Hepatocytes
Valverde A, Burks D, Fabregat I, Fisher T, Carretero J, White M, Benito M. Molecular Mechanisms of Insulin Resistance in IRS-2-Deficient Hepatocytes. Diabetes 2003, 52: 2239-2248. PMID: 12941762, DOI: 10.2337/diabetes.52.9.2239.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsAnimals, NewbornAntigens, Polyomavirus TransformingCell Line, TransformedFemaleForkhead Box Protein O1Forkhead Transcription FactorsGluconeogenesisGlucose-6-PhosphataseGlycogen SynthaseGlycogen Synthase Kinase 3HepatocytesHypoglycemic AgentsInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsIsoenzymesMaleMiceMice, Mutant StrainsPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPhosphoenolpyruvate Carboxykinase (GTP)PhosphoproteinsPregnancyProtein Kinase CProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktRetroviridaeSignal TransductionTranscription FactorsConceptsGluconeogenic gene expressionIRS-2Gene expressionPrimary hepatocytesAtypical protein kinase CIRS-1-associated phosphatidylinositolIRS-1 tyrosine phosphorylationInsulin-induced phosphatidylinositolTranslocation of phosphatidylinositolInsulin receptor substrateGlycogen synthase kinaseProtein kinase CActivation of AktDownstream phosphatidylinositolTyrosine phosphorylationPlasma membraneReceptor substrateGlycogen synthase activityMolecular mechanismsSynthase kinaseInsulin stimulationKinase CHepatocyte cell linePhosphatidylinositolFunctional insulin
1999
Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade.
Griffin ME, Marcucci MJ, Cline GW, Bell K, Barucci N, Lee D, Goodyear LJ, Kraegen EW, White MF, Shulman GI. Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade. Diabetes 1999, 48: 1270-1274. PMID: 10342815, DOI: 10.2337/diabetes.48.6.1270.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDeoxyglucoseEnzyme ActivationFatty Acids, NonesterifiedInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIsoenzymesMagnetic Resonance SpectroscopyMaleMuscle, SkeletalPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationProtein Kinase CProtein Kinase C-thetaRatsRats, Sprague-DawleySignal TransductionTyrosineZinc FingersConceptsProtein kinase C thetaGlucose transport activityInsulin resistanceMuscle glycogen synthesisFree fatty acidsC thetaInsulin-stimulated insulin receptor substrateInsulin-stimulated IRS-1 tyrosine phosphorylationTransport activityIRS-1 tyrosine phosphorylationReduced glucose transport activityInsulin-stimulated muscle glucose metabolismFatty acid-induced insulin resistance
1998
Differential Regulation of Insulin Receptor Substrate-2 and Mitogen-Activated Protein Kinase Tyrosine Phosphorylation by Phosphatidylinositol 3-Kinase Inhibitors in SH-SY5Y Human Neuroblastoma Cells*This work was supported by NIH Grants R29-NS-32843 and R01-NS-36778, grants from the American Diabetes Association and Juvenile Diabetes Foundation (to E.L.F.), and a grant from the Millie Schembechler Adrenal Research Fund of the University of Michigan Comprehensive Cancer Center (to E.L.F. and P.S.L.).
Kim B, Leventhal P, White M, Feldman E. Differential Regulation of Insulin Receptor Substrate-2 and Mitogen-Activated Protein Kinase Tyrosine Phosphorylation by Phosphatidylinositol 3-Kinase Inhibitors in SH-SY5Y Human Neuroblastoma Cells*This work was supported by NIH Grants R29-NS-32843 and R01-NS-36778, grants from the American Diabetes Association and Juvenile Diabetes Foundation (to E.L.F.), and a grant from the Millie Schembechler Adrenal Research Fund of the University of Michigan Comprehensive Cancer Center (to E.L.F. and P.S.L.). Endocrinology 1998, 139: 4881-4889. PMID: 9832424, DOI: 10.1210/endo.139.12.6348.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportCalcium-Calmodulin-Dependent Protein KinasesElectrophoresis, Polyacrylamide GelEnzyme InhibitorsGRB2 Adaptor ProteinHumansInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsIsoenzymesMitogen-Activated Protein Kinase 1NeuritesNeuroblastomaPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphoproteinsPhosphorylationProteinsShc Signaling Adaptor ProteinsSrc Homology 2 Domain-Containing, Transforming Protein 1Tumor Cells, CulturedTyrosineConceptsInsulin receptor substrate 2IRS-2 tyrosine phosphorylationMitogen-activated protein kinase activationTyrosine phosphorylationProtein kinase activationKinase activationSerine/threonine phosphorylationSubstrate 2Association of Grb2Neurite outgrowthSH-SY5Y human neuroblastomaThreonine phosphorylationNegative regulationSH-SY5Y human neuroblastoma cellsIRS-1Grb2Nervous system growthDifferential regulationPhosphorylationHuman neuroblastoma cellsNeuronal cellsPhosphatidylinositolPI 3Concentration-dependent mannerInsulin-like growth factor IInteraction of insulin receptor substrate-1 (IRS-1) with phosphatidylinositol 3-kinase: effect of substitution of serine for alanine in potential IRS-1 serine phosphorylation sites.
Delahaye L, Mothe-Satney I, Myers M, White M, Van Obberghen E. Interaction of insulin receptor substrate-1 (IRS-1) with phosphatidylinositol 3-kinase: effect of substitution of serine for alanine in potential IRS-1 serine phosphorylation sites. Endocrinology 1998, 139: 4911-9. PMID: 9832428, DOI: 10.1210/endo.139.12.6379.Peer-Reviewed Original ResearchConceptsInsulin receptor substrate-1Protein kinase B activitySerine phosphorylation sitesRegulatory subunitReceptor substrate-1Phosphorylation sitesPotential binding sitesTyrosine phosphorylationSubstrate-1Potential tyrosine phosphorylation sitesIRS-1 interactsPotential serine phosphorylation sitesWild-type IRS-1Two-hybrid systemTyrosine phosphorylation sitesInsulin-stimulated phosphatidylinositolPhosphorylate IRS-1P85alpha regulatory subunitBinding sitesYeast kinasesThreonine phosphorylationSerine mutantsYXXM motifsB activityP85alpha