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
Pulsatile Portal Vein Insulin Delivery Enhances Hepatic Insulin Action and Signaling
Matveyenko A, Liuwantara D, Gurlo T, Kirakossian D, Man C, Cobelli C, White M, Copps K, Volpi E, Fujita S, Butler P. Pulsatile Portal Vein Insulin Delivery Enhances Hepatic Insulin Action and Signaling. Diabetes 2012, 61: 2269-2279. PMID: 22688333, PMCID: PMC3425431, DOI: 10.2337/db11-1462.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2DogsForkhead Transcription FactorsGlucokinaseInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceInsulin SecretionLiverMaleNerve Tissue ProteinsPortal VeinProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleySignal TransductionConceptsPulsatile insulin secretionHepatic insulin actionInsulin secretionHepatic insulinPortal veinInsulin deliveryPulsatile patternInsulin actionDiscrete insulin secretory burstsHepatic insulin receptor substrateImpaired activationType 2 diabetes mellitusSequential liver biopsiesIntraportal insulin infusionInsulin secretory burstsHepatic insulin resistanceHepatic portal veinExpression of glucokinaseGlycemic controlDiabetes mellitusLiver biopsyInsulin resistanceInsulin infusionSecretory burstsRat modelIRS2 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
2008
Inactivation of Hepatic Foxo1 by Insulin Signaling Is Required for Adaptive Nutrient Homeostasis and Endocrine Growth Regulation
Dong X, Copps K, Guo S, Li Y, Kollipara R, DePinho R, White M. Inactivation of Hepatic Foxo1 by Insulin Signaling Is Required for Adaptive Nutrient Homeostasis and Endocrine Growth Regulation. Cell Metabolism 2008, 8: 65-76. PMID: 18590693, PMCID: PMC2929667, DOI: 10.1016/j.cmet.2008.06.006.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsEndocrine GlandsFoodForkhead Transcription FactorsGrowthHomeostasisInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsLiverMiceMice, KnockoutNerve Tissue ProteinsPhosphoproteinsSignal TransductionConceptsInsulin signalingForkhead transcription factor FOXO1Insulin-regulated glucose homeostasisExpression of genesTranscription factor FOXO1Endocrine growth regulationNutrient homeostasisMetabolic genesStress resistancePerturbed expressionActive FoxO1Growth regulationLiver-specific deletionHepatic FoxO1Hepatic insulin resistanceBody sizePI3KHepatic Irs1FOXO1TranscriptomeSomatic growthDKO miceGenesSignalingHomeostasis