2019
Phosphorylation of Forkhead Protein FoxO1 at S253 Regulates Glucose Homeostasis in Mice
Zhang K, Guo X, Yan H, Wu Y, Pan Q, Shen J, Li X, Chen Y, Li L, Qi Y, Xu Z, Xie W, Zhang W, Threadgill D, He L, Villarreal D, Sun Y, White M, Zheng H, Guo S. Phosphorylation of Forkhead Protein FoxO1 at S253 Regulates Glucose Homeostasis in Mice. Endocrinology 2019, 160: 1333-1347. PMID: 30951171, PMCID: PMC6482038, DOI: 10.1210/en.2018-00853.Peer-Reviewed Original ResearchConceptsKey phosphorylation sitesForkhead protein FoxO1Protein kinase BTranscription factor forkhead box O1Factor forkhead box O1FOXO1 nuclear localizationMultiple physiological functionsMouse Foxo1Forkhead box O1Pancreatic plasticityPhosphorylation sitesHuman FOXO1Nuclear localizationTarget genesMolecular basisS253Kinase BFoxO1 activityPhysiological functionsGlucose homeostasisBox O1Pancreatic β-cell functionFOXO1PhosphorylationHepatic glucose production
2013
Chronic 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
2005
RIP-Cre Revisited, Evidence for Impairments of Pancreatic β-Cell Function*
Lee J, Ristow M, Lin X, White M, Magnuson M, Hennighausen L. RIP-Cre Revisited, Evidence for Impairments of Pancreatic β-Cell Function*. Journal Of Biological Chemistry 2005, 281: 2649-2653. PMID: 16326700, DOI: 10.1074/jbc.m512373200.Peer-Reviewed Original ResearchConceptsRIP-Cre miceRIP-CreGlucose intolerancePancreatic β-cell functionΒ-cell functionFrank diabetesInsulin secretionRat insulin II gene promoterTransgenic miceMiceCre recombinaseIntoleranceMolecular underpinningsConditional geneDiabetesGene promoterGenetic pathwaysCre/loxP recombinase systemGenesLoxP sitesImpairmentRecombinase systemSecretion
1998
Disruption of IRS-2 causes type 2 diabetes in mice
Withers D, Gutierrez J, Towery H, Burks D, Ren J, Previs S, Zhang Y, Bernal D, Pons S, Shulman G, Bonner-Weir S, White M. Disruption of IRS-2 causes type 2 diabetes in mice. Nature 1998, 391: 900-904. PMID: 9495343, DOI: 10.1038/36116.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseCloning, MolecularDiabetes Mellitus, Type 2FemaleGene TargetingHumansInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsIslets of LangerhansLiverMaleMiceMice, Inbred C57BLMuscle, SkeletalPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationReceptor, InsulinRecombination, GeneticSignal TransductionConceptsType 2 diabetesInsulin resistanceHuman type 2 diabetesPancreatic β-cell functionInsulin secretion increasesSingle molecular abnormalityΒ-cell compensationIRS-2-deficient miceΒ-cell functionHuman type 2Insulin secretionInsulin receptor substrateGlucose homeostasisSecretion increasesInsulin actionType 2DiabetesMolecular abnormalitiesProgressive deteriorationSkeletal muscleIRS-2Insulin signalingIRS-1Mild resistanceMice