2020
From population to neuron: exploring common mediators for metabolic problems and mental illnesses
Takayanagi Y, Ishizuka K, Laursen T, Yukitake H, Yang K, Cascella N, Ueda S, Sumitomo A, Narita Z, Horiuchi Y, Niwa M, Taguchi A, White M, Eaton W, Mortensen P, Sakurai T, Sawa A. From population to neuron: exploring common mediators for metabolic problems and mental illnesses. Molecular Psychiatry 2020, 26: 3931-3942. PMID: 33173197, PMCID: PMC8514126, DOI: 10.1038/s41380-020-00939-5.Peer-Reviewed Original ResearchConceptsMajor mental illnessOlfactory neuronal cellsInsulin resistanceMental illnessBipolar disorderNeuronal cellsPathophysiological mediatorsHigh incidenceSZ patientsCommon mediatorIrs2 knockout miceSame large cohortIRS2 tyrosine phosphorylationDanish registriesBP patientsHealthy controlsHealthy subjectsLarge cohortEpidemiological dataEpidemiological studiesKnockout miceAnimal modelsPatientsMetabolic problemsDiabetesParaventricular, 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 perspective
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
2003
Insulin Receptor Substrate-2 Deficiency Impairs Brain Growth and Promotes Tau Phosphorylation
Schubert M, Brazil D, Burks D, Kushner J, Ye J, Flint C, Farhang-Fallah J, Dikkes P, Warot X, Rio C, Corfas G, White M. Insulin Receptor Substrate-2 Deficiency Impairs Brain Growth and Promotes Tau Phosphorylation. Journal Of Neuroscience 2003, 23: 7084-7092. PMID: 12904469, PMCID: PMC6740672, DOI: 10.1523/jneurosci.23-18-07084.2003.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsApoptosisBody WeightBrainCell CountCell DivisionCell SurvivalCells, CulturedCerebellumCrosses, GeneticEnzyme InhibitorsHeterozygoteIn Situ Nick-End LabelingInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutNeuronsOrgan SizePhosphoproteinsPhosphorylationReceptor, IGF Type 1Signal TransductionTau ProteinsConceptsMolecular linkInsulin receptor substrate (IRS) proteinsBrain growthNeurodegenerative diseasesPancreatic beta-cell functionPeripheral insulin actionSubstrate proteinsBeta-cell functionTyrosine phosphorylationLike growth factorIrs2 branchInsulin resistanceTau phosphorylationIRS2 geneNeuronal proliferationInsulin actionMouse brainInsulin-IGFGrowth factorPhosphorylationIRS2DiabetesBody growthDiseaseMice