2021
Irs2 deficiency alters hippocampus-associated behaviors during young adulthood
Tanokashira D, Wang W, Maruyama M, Kuroiwa C, White M, Taguchi A. Irs2 deficiency alters hippocampus-associated behaviors during young adulthood. Biochemical And Biophysical Research Communications 2021, 559: 148-154. PMID: 33940386, PMCID: PMC8361845, DOI: 10.1016/j.bbrc.2021.04.101.Peer-Reviewed Original ResearchConceptsYoung adult male miceAdult male miceMale miceAlzheimer's diseaseType 2 diabetes mellitusInsulin-like growth factor-1Brain energy metabolismGrowth factor-1Young adult malesCore body temperatureDiabetes mellitusInsulin resistanceInsulin/insulin-like growth factor-1Risk factorsBehavioral alterationsCognitive impairmentGenetic backgroundPremature deathHippocampusMiceYoung adulthoodAberrant alterationsFactor 1Abnormal changesBody temperature
2020
Paraventricular, subparaventricular and periventricular hypothalamic IRS4-expressing neurons are required for normal energy balance
Sutton A, Gonzalez I, Sadagurski M, Rajala M, Lu C, Allison M, Adams J, Myers M, White M, Olson D. Paraventricular, subparaventricular and periventricular hypothalamic IRS4-expressing neurons are required for normal energy balance. Scientific Reports 2020, 10: 5546. PMID: 32218485, PMCID: PMC7099088, DOI: 10.1038/s41598-020-62468-z.Peer-Reviewed Original ResearchConceptsEnergy expenditureEnergy expenditure regulationAnti-obesity therapiesFeeding-related behaviorsNormal energy balanceInsulin receptor substrate 4Negative energy balancePVH neuronsHypothalamic circuitryHypothalamic sitesEnergy balance controlFeeding suppressionParaventricular nucleusSatiety responseSubstantial obesityNormal feedingPVHNeuronsViral toolsNeural componentsHindbrain regionsObesityRequisite roleBalance controlEnergy balance
2014
IRS2 integrates insulin/IGF1 signalling with metabolism, neurodegeneration and longevity
White M. IRS2 integrates insulin/IGF1 signalling with metabolism, neurodegeneration and longevity. Diabetes Obesity And Metabolism 2014, 16: 4-15. PMID: 25200290, DOI: 10.1111/dom.12347.Peer-Reviewed Original ResearchConceptsInsulin/IGF1Central nervous systemInsulin-like signalingLife spanOrganisms showsCellular functionsNutrient homeostasisInsulin resistanceGenetic manipulationSystemic insulin resistanceClinical Alzheimer's diseaseType 2 diabetesEnergy homeostasisNeurodegenerative diseasesMetabolismNeurodegenerationCompensatory hyperinsulinaemiaHomeostasisProgressive neurodegenerationSystemic metabolismIGF1Excess insulinNervous systemAlzheimer's diseaseClinical perspectiveInsulin Receptor Substrates Are Essential for the Bioenergetic and Hypertrophic Response of the Heart to Exercise Training
Riehle C, Wende A, Zhu Y, Oliveira K, Pereira R, Jaishy B, Bevins J, Valdez S, Noh J, Kim B, Moreira A, Weatherford E, Manivel R, Rawlings T, Rech M, White M, Abel E. Insulin Receptor Substrates Are Essential for the Bioenergetic and Hypertrophic Response of the Heart to Exercise Training. Molecular And Cellular Biology 2014, 34: 3450-3460. PMID: 25002528, PMCID: PMC4135616, DOI: 10.1128/mcb.00426-14.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEnergy MetabolismGene Expression RegulationGlycogenHeartInsulin Receptor Substrate ProteinsMiceMice, Inbred C57BLMice, KnockoutMitochondriaPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPhosphatidylinositol 3-KinasesProtein IsoformsSignal TransductionSwimmingTranscription FactorsConceptsInsulin receptor substrate-1IRS isoformsProtein phosphatase 2AReceptor substrate-1Insulin receptor substrateInsulin-like growth factor 1 receptorGrowth factor 1 receptorSynthase kinase-3βPeroxisome proliferator-activated receptor gamma coactivatorPhosphatase 2AProliferator-activated receptor gamma coactivatorFactor 1 receptorPGC-1α protein contentCardiomyocyte-specific deletionDevelopmental regulationProtein contentHypertrophic responseReceptor substrateReceptor gamma coactivatorFatty acid oxidationSubstrate-1Kinase-3βDivergent rolesMetabolic adaptationNonredundant role
2013
Myocardial Loss of IRS1 and IRS2 Causes Heart Failure and Is Controlled by p38α MAPK During Insulin Resistance
Qi Y, Xu Z, Zhu Q, Thomas C, Kumar R, Feng H, Dostal D, White M, Baker K, Guo S. Myocardial Loss of IRS1 and IRS2 Causes Heart Failure and Is Controlled by p38α MAPK During Insulin Resistance. Diabetes 2013, 62: 3887-3900. PMID: 24159000, PMCID: PMC3806607, DOI: 10.2337/db13-0095.Peer-Reviewed Original ResearchConceptsIRS2 proteinGene expressionType 2 diabetesEnergy metabolism gene expressionInsulin resistanceMetabolic gene expressionBox class ODouble knockout miceHeart failureActivation of p38Chronic insulin exposureActivation of p38αMetabolism gene expressionProtein kinaseRole of IRS1Cellular metabolismMolecular mechanismsInsulin receptorNeonatal rat ventricular cardiomyocytesP38α MAPKCause heart failureCellular dysfunctionIRS1Myocardial insulin resistanceClass O
2012
IRS2 Signaling in LepR-b Neurons Suppresses FoxO1 to Control Energy Balance Independently of Leptin Action
Sadagurski M, Leshan R, Patterson C, Rozzo A, Kuznetsova A, Skorupski J, Jones J, Depinho R, Myers M, White M. IRS2 Signaling in LepR-b Neurons Suppresses FoxO1 to Control Energy Balance Independently of Leptin Action. Cell Metabolism 2012, 15: 703-712. PMID: 22560222, PMCID: PMC3361909, DOI: 10.1016/j.cmet.2012.04.011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCytoskeletal ProteinsEnergy MetabolismFemaleForkhead Box Protein O1Forkhead Transcription FactorsGene ExpressionGlucoseGlucose IntoleranceHomeostasisInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceLeptinMaleMiceMice, TransgenicNerve Tissue ProteinsNeuronsObesityReceptors, LeptinSignal TransductionConceptsLeptin actionGlucose homeostasisGlucose intoleranceInsulin resistanceHormone leptinFoxO1 nuclear exclusionIRS2 expressionLeptin receptorMetabolic actionsNeuronsMiceEnergy balanceFOXO1Metabolic sensingIRS2HomeostasisGene expressionNuclear exclusionObesityLeptinExpressionCNSInsulinIntoleranceBrain
2000
IRS-2 pathways integrate female reproduction and energy homeostasis
Burks D, de Mora J, Schubert M, Withers D, Myers M, Towery H, Altamuro S, Flint C, White M. IRS-2 pathways integrate female reproduction and energy homeostasis. Nature 2000, 407: 377-382. PMID: 11014193, DOI: 10.1038/35030105.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEnergy IntakeEnergy MetabolismEstrusFemaleFertilityGonadal Steroid HormonesHomeostasisInfertilityInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsLeptinLuteinizing HormoneMaleMiceMice, Inbred C57BLMice, KnockoutOvaryPhosphoproteinsPituitary GlandReceptor, InsulinReproductionSignal TransductionSteroidsConceptsInsulin receptor substrate 2Insulin/insulin-like growth factor-1Insulin-signaling pathwayEnergy homeostasisC. elegansIRS-2 pathwayLower organismsSubstrate 2Female reproductionRegulation of fertilityMetabolic signalsInsulin-like growth factor-1Reproductive statusFactor 1Infertile conditionsSevere dietary restrictionMammalsGrowth factor-1HomeostasisReproductionAnovulatory ovariesHypothalamic controlFemale infertilityPlasma concentrationsCatabolic state