2013
Genetic Inactivation of Pyruvate Dehydrogenase Kinases Improves Hepatic Insulin Resistance Induced Diabetes
Tao R, Xiong X, Harris R, White M, Dong X. Genetic Inactivation of Pyruvate Dehydrogenase Kinases Improves Hepatic Insulin Resistance Induced Diabetes. PLOS ONE 2013, 8: e71997. PMID: 23940800, PMCID: PMC3733847, DOI: 10.1371/journal.pone.0071997.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDiabetes Mellitus, ExperimentalGene Expression Regulation, EnzymologicGene SilencingGlucose IntoleranceGlucose Tolerance TestInsulin Receptor Substrate ProteinsInsulin ResistanceLiverMiceMice, KnockoutOrgan SpecificityProtein Serine-Threonine KinasesPyruvate Dehydrogenase Acetyl-Transferring KinaseConceptsPyruvate dehydrogenase kinasePDK4 geneGene knockdownDehydrogenase kinasePDK4 gene expressionMitochondrial pyruvate dehydrogenasePdk geneGene attributesPDK2 genesGene inactivationGene expressionGenetic inactivationPyruvate dehydrogenaseGenesInsulin receptorMetabolic analysisSpecific shRNAGene deletionGenetic backgroundHepatic insulin receptorNull miceKinasePDK2KnockdownCritical roleChronic 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
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 modelkNOXing on the Door of Selective Insulin Resistance
Cheng Z, White M. kNOXing on the Door of Selective Insulin Resistance. Arteriosclerosis Thrombosis And Vascular Biology 2012, 32: 1063-1065. PMID: 22517360, PMCID: PMC3996730, DOI: 10.1161/atvbaha.112.246868.Peer-Reviewed Original ResearchAnimalsDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2InsulinInsulin ResistanceNADPH Oxidase 4NADPH Oxidases
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
2003
Upregulation of insulin receptor substrate-2 in pancreatic β cells prevents diabetes
Hennige A, Burks D, Ozcan U, Kulkarni R, Ye J, Park S, Schubert M, Fisher T, Dow M, Leshan R, Zakaria M, Mossa-Basha M, White M. Upregulation of insulin receptor substrate-2 in pancreatic β cells prevents diabetes. Journal Of Clinical Investigation 2003, 112: 1521-1532. PMID: 14617753, PMCID: PMC259126, DOI: 10.1172/jci18581.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell SizeDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Dietary FatsGene Expression RegulationHumansInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsIslets of LangerhansIslets of Langerhans TransplantationMaleMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicPhosphoproteinsReceptor, InsulinSignal TransductionSurvival RateUp-RegulationConceptsPancreatic beta-cell functionPeripheral insulin actionBeta-cell failureBeta-cell functionType 2 diabetesIrs2-/- miceInsulin receptor substrate 2Beta-cell growthBeta cell-specific expressionPrevents diabetesObese miceTransgenic isletsInsulin secretionWT isletsIRS2 expressionPharmacological approachesBeta cellsPhysiologic responsesInsulin actionRational treatmentDiabetesInsulin/IGFCell functionMiceCell-specific expression