2014
Insulin and Metabolic Stress Stimulate Multisite Serine/Threonine Phosphorylation of Insulin Receptor Substrate 1 and Inhibit Tyrosine Phosphorylation*
Hançer N, Qiu W, Cherella C, Li Y, Copps K, White M. Insulin and Metabolic Stress Stimulate Multisite Serine/Threonine Phosphorylation of Insulin Receptor Substrate 1 and Inhibit Tyrosine Phosphorylation*. Journal Of Biological Chemistry 2014, 289: 12467-12484. PMID: 24652289, PMCID: PMC4007441, DOI: 10.1074/jbc.m114.554162.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnisomycinAntigens, CDBlotting, WesternCHO CellsCricetinaeCricetulusEnzyme InhibitorsHumansHypoglycemic AgentsInsulinInsulin Receptor Substrate ProteinsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktRatsReceptor, InsulinRibosomal Protein S6 Kinases, 70-kDaSerineSignal TransductionThapsigarginThreonineTOR Serine-Threonine KinasesTunicamycinTyrosineConceptsTyrosine phosphorylationPhospho-specific monoclonal antibodiesSerine/threonine phosphorylationInsulin receptor tyrosine kinasePI3KInsulin receptor substrate-1Insulin-stimulated cellsHuman insulin receptorIRS1 tyrosine phosphorylationReceptor substrate-1Metabolic stressReceptor tyrosine kinasesThreonine phosphorylationThreonine residuesS6 kinasePI3K inhibitionSubstrate-1Mechanistic targetTyrosine kinaseInsulin stimulationMEK pathwayKey substrateInsulin receptorPresence of inhibitorsCHO cells
2013
Chronic activation of a designer Gq-coupled receptor improves β cell function
Jain S, de Azua I, Lu H, White M, Guettier J, Wess J. Chronic activation of a designer Gq-coupled receptor improves β cell function. Journal Of Clinical Investigation 2013, 123: 1750-1762. PMID: 23478411, PMCID: PMC3613926, DOI: 10.1172/jci66432.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell ProliferationClozapineDiabetes Mellitus, ExperimentalDrug Evaluation, PreclinicalFemaleGene ExpressionGTP-Binding Protein alpha Subunits, Gq-G11Hypoglycemic AgentsInsulin Receptor Substrate ProteinsInsulin-Secreting CellsMaleMAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, TransgenicMolecular Targeted TherapyMuscarinic AgonistsProtein EngineeringReceptor, Muscarinic M3Receptors, G-Protein-CoupledRecombinant ProteinsConceptsΒ-cell functionΒ-cellsCell functionPancreatic β-cell functionStreptozotocin-induced diabetesBeneficial metabolic effectsTreatment of T2D.High-fat dietType 2 diabetesNovel antidiabetic drugsType G proteinsClasses of receptorsChronic stimulationMetabolic deficitsAntidiabetic drugsMetabolic effectsChronic activationGlucose homeostasisTherapeutic strategiesCell pathwaysEnhanced expressionReceptorsNumerous receptorsCellular effectsDiabetes
2009
Metformin and Insulin Meet in a Most Atypical Way
White M. Metformin and Insulin Meet in a Most Atypical Way. Cell Metabolism 2009, 9: 485-487. PMID: 19490902, DOI: 10.1016/j.cmet.2009.05.007.Peer-Reviewed Original ResearchBreathing Room: The (Un)Natural History of Adipose Microhypoxia and Insulin Resistance
Copps K, White M. Breathing Room: The (Un)Natural History of Adipose Microhypoxia and Insulin Resistance. Diabetes 2009, 58: 26-27. PMID: 19114728, PMCID: PMC2606882, DOI: 10.2337/db08-1517.Peer-Reviewed Original Research
2005
Attenuation of Accumulation of Neointimal Lipid by Pioglitazone in Mice Genetically Deficient in Insulin Receptor Substrate-2 and Apolipoprotein E
Clough M, Schneider D, Sobel B, White M, Wadsworth M, Taatjes D. Attenuation of Accumulation of Neointimal Lipid by Pioglitazone in Mice Genetically Deficient in Insulin Receptor Substrate-2 and Apolipoprotein E. Journal Of Histochemistry & Cytochemistry 2005, 53: 603-610. PMID: 15872053, DOI: 10.1369/jhc.4a6590.2005.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAnimalsAortaApolipoproteins EArteriosclerosisHyperlipidemiasHypoglycemic AgentsInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsLipid MetabolismMiceMice, Inbred C57BLMice, KnockoutPhosphoproteinsPioglitazoneReceptor, InsulinThiazolidinedionesTunica IntimaConceptsInsulin resistanceApolipoprotein EAcute coronary syndromeVulnerable atherosclerotic plaquesInsulin receptor substrate 2Accumulation of lipidsCoronary syndromeProximal aortaInsulin sensitizersNeointimal accumulationAtheroma formationAortic intimaAtherosclerotic lesionsAtherosclerotic plaquesType 2PioglitazoneMiceLesionsCross-sectional areaHeterozygous deficiencyAtherogenesisSubstrate 2TreatmentLipidsAtheroma
2004
IRS‐2 mediates the antiapoptotic effect of insulin in neonatal hepatocytes
Valverde A, Fabregat I, Burks D, White M, Benito M. IRS‐2 mediates the antiapoptotic effect of insulin in neonatal hepatocytes. Hepatology 2004, 40: 1285-1294. PMID: 15565601, DOI: 10.1002/hep.20485.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornApoptosisApoptosis Regulatory ProteinsBcl-2-Like Protein 11Bcl-X ProteinBlood ProteinsCarrier ProteinsEpidermal Growth FactorFemaleForkhead Box Protein O1Forkhead Transcription FactorsGene ExpressionHepatocytesHypoglycemic AgentsInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMaleMembrane ProteinsMiceMice, Mutant StrainsPhosphatidylinositol 3-KinasesPhosphoproteinsPregnancyProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-bcl-2Signal TransductionTranscription FactorsConceptsCaspase-3 activityIRS-2Caspase-3 activationGene expressionWild-type hepatocytesDominant negative FoxO1Wild-type cellsSerum withdrawal-induced apoptosisInsulin receptor substrateWithdrawal-induced apoptosisAnti-apoptotic gene expressionImmortalized hepatocyte cell linesIRS-2 signalingPIP3 generationProapoptotic gene expressionAntiapoptotic gene expressionProlonged insulin treatmentEpidermal growth factorActive FoxO1Receptor substrateNeonatal hepatocytesProapoptotic genesAntiapoptotic genesCaspase-8Serum withdrawal
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
2000
IRS-4 Mediates Protein Kinase B Signaling during Insulin Stimulation without Promoting Antiapoptosis
Uchida T, Myers M, White M. IRS-4 Mediates Protein Kinase B Signaling during Insulin Stimulation without Promoting Antiapoptosis. Molecular And Cellular Biology 2000, 20: 126-138. PMID: 10594015, PMCID: PMC85068, DOI: 10.1128/mcb.20.1.126-138.2000.Peer-Reviewed Original ResearchConceptsPKB/AktProtein kinase BIRS-1IRS-2IRS-4Insulin stimulationGrb-2Bad phosphorylationInsulin-stimulated mitogen-activated protein kinase activityInsulin receptor substrate (IRS) proteinsProtein kinase B signalingMitogen-activated protein kinase activityProtein kinase activityHuman insulin receptorPhosphorylation of BadKinase B signalingSubstrate proteinsMyeloid progenitor cellsApoptosis of cellsKinase activityKinase BPhosphatidylinositolInsulin receptorInterleukin-3Phosphorylation