2018
Ablation of insulin receptor substrates 1 and 2 suppresses Kras-driven lung tumorigenesis
Xu H, Lee M, Tsai P, Adler A, Curry N, Challa S, Freinkman E, Hitchcock D, Copps K, White M, Bronson R, Marcotrigiano M, Wu Y, Clish C, Kalaany N. Ablation of insulin receptor substrates 1 and 2 suppresses Kras-driven lung tumorigenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: 4228-4233. PMID: 29610318, PMCID: PMC5910837, DOI: 10.1073/pnas.1718414115.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsAmino AcidsAnimalsAutophagyCarcinogenesisCarcinoma, Non-Small-Cell LungCodon, TerminatorGenes, rasHumansInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor ILung NeoplasmsMiceNeoplasm ProteinsProteolysisProto-Oncogene Proteins c-aktProto-Oncogene Proteins p21(ras)Signal TransductionConceptsIR/IGF1RLung cancerLung tumorigenesisInsulin receptorTumor cellsInsulin-like growth factor 1 receptorCell lung cancerGrowth factor 1 receptorHuman NSCLC cellsEffective therapeutic strategyLung cancer initiationIntracellular levelsKirsten rat sarcomaFactor 1 receptorTumor burdenCancer deathLeading causeMutant NSCLCNSCLC cellsIGF1R inhibitionMouse modelTherapeutic strategiesInsulin/IGF1Acute lossRat sarcoma
2011
IRS2 increases mitochondrial dysfunction and oxidative stress in a mouse model of Huntington disease
Sadagurski M, Cheng Z, Rozzo A, Palazzolo I, Kelley G, Dong X, Krainc D, White M. IRS2 increases mitochondrial dysfunction and oxidative stress in a mouse model of Huntington disease. Journal Of Clinical Investigation 2011, 121: 4070-4081. PMID: 21926467, PMCID: PMC3195462, DOI: 10.1172/jci46305.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsBrainDisease Models, AnimalDisease ProgressionFemaleForkhead Box Protein O1Forkhead Transcription FactorsGene ExpressionHumansHuntington DiseaseInsulin Receptor Substrate ProteinsLongevityMaleMiceMice, KnockoutMice, Mutant StrainsMice, TransgenicMitochondriaOxidative StressSignal TransductionConceptsHuntington's diseaseOxidative stressMouse modelProgression of HDMitochondrial dysfunctionMajor risk factorR6/2 mouse modelNeuronal oxidative stressMitochondrial functionHD-like symptomsHD patientsNumber of autophagosomesTranscription factor FOXO1Risk factorsR6/2 miceSlow progressionTherapeutic approachesExpression of IRS2HD progressionLife spanNeurodegenerative diseasesIRS2 levelsProgressionDiseaseMiceRegulation of glucose homeostasis through a XBP-1–FoxO1 interaction
Zhou Y, Lee J, Reno C, Sun C, Park S, Chung J, Lee J, Fisher S, White M, Biddinger S, Ozcan U. Regulation of glucose homeostasis through a XBP-1–FoxO1 interaction. Nature Medicine 2011, 17: 356-365. PMID: 21317886, PMCID: PMC3897616, DOI: 10.1038/nm.2293.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseDisease Models, AnimalDNA-Binding ProteinsForkhead Box Protein O1Forkhead Transcription FactorsGlucoseHomeostasisHydrolysisInsulin ResistanceLiverMiceMutationPhosphorylationReceptor, InsulinRegulatory Factor X Transcription FactorsSignal TransductionTranscription FactorsX-Box Binding Protein 1
2010
Targeting Forkhead Box O1 from the Concept to Metabolic Diseases: Lessons from Mouse Models
Cheng Z, White M. Targeting Forkhead Box O1 from the Concept to Metabolic Diseases: Lessons from Mouse Models. Antioxidants & Redox Signaling 2010, 14: 649-661. PMID: 20615072, PMCID: PMC3025764, DOI: 10.1089/ars.2010.3370.Peer-Reviewed Original ResearchConceptsForkhead box O (FOXO) transcription factorsInsulin receptor substratePhosphoenolpyruvate carboxykinaseActivation of FOXO1Β-cellsRegulation of metabolismAkt signal cascadeRole of FoxO1Transcriptional regulationForkhead box O1Β-cell proliferationStress resistanceTranscription factorsDuodenal homeobox 1Mitochondrial metabolismPancreatic β-cellsReceptor substrateSignal cascadeΒ-cell failureLipid switchesCarboxypeptidase E.Mouse modelHomeobox 1Metabolic diseasesInhibition of FOXO1Extreme makeover of pancreatic α-cells
Zaret K, White M. Extreme makeover of pancreatic α-cells. Nature 2010, 464: 1132-1133. PMID: 20414295, PMCID: PMC3982719, DOI: 10.1038/4641132a.Peer-Reviewed Original Research
2008
Genetic Deficiency of Glycogen Synthase Kinase-3β Corrects Diabetes in Mouse Models of Insulin Resistance
Tanabe K, Liu Z, Patel S, Doble B, Li L, Cras-Méneur C, Martinez S, Welling C, White M, Bernal-Mizrachi E, Woodgett J, Permutt M. Genetic Deficiency of Glycogen Synthase Kinase-3β Corrects Diabetes in Mouse Models of Insulin Resistance. PLOS Biology 2008, 6: e37. PMID: 18288891, PMCID: PMC2245985, DOI: 10.1371/journal.pbio.0060037.Peer-Reviewed Original ResearchConceptsBeta-cell massIrs2-/- miceInsulin resistanceMouse modelType 2 diabetes mellitusObese insulin-resistant individualsWhole-body glucose disposalOnset of diabetesPdx1 levelsBeta-cell functionBeta-cell lossInsulin-resistant individualsBeta-cell replicationGSK-3betaBeta-cell proliferationInsulin receptor substrate 2Cyclin-dependent kinase inhibitorDiabetes mellitusDiabetes onsetEarly diabetesPI-3K/Akt pathwayGlucose disposalGSK-3beta activityDiabetesInsulin action