2017
Endotoxemia-mediated activation of acetyltransferase P300 impairs insulin signaling in obesity
Cao J, Peng J, An H, He Q, Boronina T, Guo S, White M, Cole P, He L. Endotoxemia-mediated activation of acetyltransferase P300 impairs insulin signaling in obesity. Nature Communications 2017, 8: 131. PMID: 28743992, PMCID: PMC5526866, DOI: 10.1038/s41467-017-00163-w.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorE1A-Associated p300 ProteinEndoplasmic Reticulum StressEndotoxemiaGene Expression ProfilingImmunoblottingInsulinInsulin ResistanceLipopolysaccharidesLiverMaleMembrane ProteinsMice, Inbred C57BLMice, ObeseObesityProtein Serine-Threonine KinasesReceptor, InsulinSignal TransductionX-Box Binding Protein 1ConceptsInsulin resistanceP300 acetyltransferase activityHigh-fat diet-fedChronic low-grade inflammationObese ob/ob miceOb/ob miceLow-grade inflammationDiet-induced obesityAcetyltransferase activityElevated plasma concentrationsPromising therapeutic targetCytoplasm of hepatocytesEndoplasmic reticulum stressObese patientsObese miceInsulin sensitivityIntestinal permeabilityOb micePlasma concentrationsDisrupts insulinTherapeutic targetImpairs insulinPharmacological inhibitionGlucose productionObesity
2016
Insulin receptor substrate-1 deficiency drives a proinflammatory phenotype in KRAS mutant lung adenocarcinoma
Metz H, Kargl J, Busch S, Kim K, Kurland B, Abberbock S, Randolph-Habecker J, Knoblaugh S, Kolls J, White M, Houghton A. Insulin receptor substrate-1 deficiency drives a proinflammatory phenotype in KRAS mutant lung adenocarcinoma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 8795-8800. PMID: 27439864, PMCID: PMC4978299, DOI: 10.1073/pnas.1601989113.Peer-Reviewed Original ResearchConceptsInsulin receptor substrate-1Janus kinase/signal transducerKinase/signal transducerTumor burdenActivator of transcriptionReceptor substrate-1IRS-1 deficiencyKRAS-mutant lung adenocarcinomaInsulin-like growth factor receptorAdenoviral Cre recombinaseIL-22 receptorMutant lung adenocarcinomaTumor-promoting inflammationAdaptor proteinSignificant survival disadvantageGrowth factor receptorSignal transducerSubstrate-1PI3KProinflammatory phenotypeLung cancerLung adenocarcinomaMutant subgroupTissue microarrayCre recombinase
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
2008
Irs2 Inactivation Suppresses Tumor Progression in Pten +/− Mice
Szabolcs M, Keniry M, Simpson L, Reid L, Koujak S, Schiff S, Davidian G, Licata S, Gruvberger-Saal S, Murty V, Nandula S, Efstratiadis A, Kushner J, White M, Parsons R. Irs2 Inactivation Suppresses Tumor Progression in Pten +/− Mice. American Journal Of Pathology 2008, 174: 276-286. PMID: 19095950, PMCID: PMC2631340, DOI: 10.2353/ajpath.2009.080086.Peer-Reviewed Original ResearchConceptsPI3KInsulin receptor substrate-2 expressionProstatic intraepithelial neoplasiaHuman prostate cancerCancer cell growthSuppresses tumor progressionIntraepithelial neoplasiaInitiation of neoplasiaProstate cancerIRS2 expressionMultiple organsExpression of MYCTumor progressionTumor samplesMiceHuman cancersMYC expressionProgressionExpression levelsPTEN levelsBasement membraneIRS2NeoplasiaTumorsCancer
2006
Suppression of Insulin Receptor Substrate 1 (IRS-1) Promotes Mammary Tumor Metastasis
Ma Z, Gibson S, Byrne M, Zhang J, White M, Shaw L. Suppression of Insulin Receptor Substrate 1 (IRS-1) Promotes Mammary Tumor Metastasis. Molecular And Cellular Biology 2006, 26: 9338-9351. PMID: 17030605, PMCID: PMC1698550, DOI: 10.1128/mcb.01032-06.Peer-Reviewed Original ResearchConceptsIRS-1Insulin receptor substrate (IRS) proteinsInsulin receptor substrate-1Wild-type levelsMetastasis suppressor functionReceptor substrate-1Cell surface receptorsBreast cancerSubstrate proteinsCytoplasmic adaptorAkt/mTOR activityMammary tumor metastasisSignificant homologySerine phosphorylationDistinct functionsSubstrate-1Mammary tumorsIRS-2MTOR activitySuppressor functionMetastatic mammary tumorsTumor cellsIR-1Surface receptorsBreast cancer metastasis
2004
Involvement of Insulin Receptor Substrate 2 in Mammary Tumor Metastasis
Nagle J, Ma Z, Byrne M, White M, Shaw L. Involvement of Insulin Receptor Substrate 2 in Mammary Tumor Metastasis. Molecular And Cellular Biology 2004, 24: 9726-9735. PMID: 15509777, PMCID: PMC525494, DOI: 10.1128/mcb.24.22.9726-9735.2004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBase SequenceBreast NeoplasmsCell Line, TumorDNA, NeoplasmFemaleHumansInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMammary Neoplasms, ExperimentalMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMitosisNeoplasm InvasivenessPhosphoproteinsPhosphorylationConceptsIRS-2Insulin receptor substrate (IRS) proteinsMammary tumor cellsPolyoma virus middle T antigenInsulin receptor substrate 2Middle T antigenGrowth factor deprivationTumor cellsIRS-2 expressionSubstrate proteinsPyV mTMammary tumor metastasisApoptotic stimuliFactor deprivationAdaptor moleculeIncidence of metastasisMitotic cellsMammary fat padMammary tumor progressionBreast cancer metastasisHuman breast cancerSubstrate 2T antigenTumor initiationCancer metastasis
2003
Role of Insulin Receptor Substrates and Protein Kinase C-ζ in Vascular Permeability Factor/Vascular Endothelial Growth Factor Expression in Pancreatic Cancer Cells*
Neid M, Datta K, Stephan S, Khanna I, Pal S, Shaw L, White M, Mukhopadhyay D. Role of Insulin Receptor Substrates and Protein Kinase C-ζ in Vascular Permeability Factor/Vascular Endothelial Growth Factor Expression in Pancreatic Cancer Cells*. Journal Of Biological Chemistry 2003, 279: 3941-3948. PMID: 14604996, DOI: 10.1074/jbc.m303975200.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaBase SequenceCell Line, TumorDNA, NeoplasmFeedbackGene Expression Regulation, NeoplasticHumansInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsNeovascularization, PathologicPancreatic NeoplasmsPhosphoproteinsProtein Kinase CSignal TransductionSp1 Transcription FactorVascular Endothelial Growth Factor AConceptsVPF/VEGF expressionIRS proteinsIRS-2Negative feedback loopVEGF transcriptionPKC-zetaVascular Permeability Factor/Vascular Endothelial Growth Factor ExpressionPancreatic cancer cellsProtein kinase C zetaCancer cellsInsulin receptor substrate-1IGF-1RReceptor substrate-1Insulin receptor substrateIRS-2 proteinProtein kinase CMajor downstream moleculesInsulin-like growth factor receptorRenal cancer cellsVascular permeability factor/vascular endothelial growth factorIGF-1R signalingGrowth factorRas pathwayGrowth factor receptorC zeta