2019
282-LB: Dysregulated FGF21 Links Hepatic Insulin Resistance to Dysfunctional BAT
STOEHR O, TAO R, COPPS K, WHITE M. 282-LB: Dysregulated FGF21 Links Hepatic Insulin Resistance to Dysfunctional BAT. Diabetes 2019, 68 DOI: 10.2337/db19-282-lb.Peer-Reviewed Original ResearchHepatic insulin resistanceFGF-21Insulin resistanceHFD feedingControl miceDiabetic phenotypeGlucose metabolismFGF-21 serum levelsWhole-body glucose metabolismGlucose uptakeInsulin-resistant liverImproved glucose toleranceWild-type miceHepatic glucose productionSevere diabetic phenotypeNormal glucose uptakeHealthy batsBAT dysfunctionSerum levelsGlucose toleranceBAT functionType miceNormal rangeInsulin actionAdenoviral infection
2018
Metabolic Dysfunction within Brown Adipose Tissue and Skeletal Muscle Caused by Complete Hepatic Insulin Resistance Is Reversible by FGF-21 Treatment
STOEHR O, TAO R, COPPS K, WHITE M. Metabolic Dysfunction within Brown Adipose Tissue and Skeletal Muscle Caused by Complete Hepatic Insulin Resistance Is Reversible by FGF-21 Treatment. Diabetes 2018, 67 DOI: 10.2337/db18-1873-p.Peer-Reviewed Original ResearchHepatic insulin resistanceFGF-21Insulin resistanceGlucose toleranceSkeletal muscleGlucose uptakeAdipose tissue markersFGF-21 treatmentSkeletal muscle dysfunctionSystemic insulin resistanceBetter glucose toleranceSystemic glucose homeostasisDouble knockout miceBrown adipose tissueDeletion of FoxO1Hepatokine secretionThermogenesis markersHepatic infectionBody core temperatureGlucose intoleranceMuscle dysfunctionSevere hyperglycemiaControl miceInsulin sensitivityMetabolic dysfunctionInactivating hepatic follistatin alleviates hyperglycemia
Tao R, Wang C, Stöhr O, Qiu W, Hu Y, Miao J, Dong X, Leng S, Stefater M, Stylopoulos N, Lin L, Copps K, White M. Inactivating hepatic follistatin alleviates hyperglycemia. Nature Medicine 2018, 24: 1058-1069. PMID: 29867232, PMCID: PMC6039237, DOI: 10.1038/s41591-018-0048-0.Peer-Reviewed Original ResearchConceptsHepatic glucose productionAdipose tissue insulinGlucose toleranceTissue insulinSuppression of HGPGastric bypass surgeryFed obese miceHepatic insulin resistanceWhite adipose tissuePotential clinical significanceInsulin receptor substrate-1Bypass surgeryGlucose intoleranceHepatic inactivationObese miceInsulin resistanceObese individualsGlycated hemoglobinTranscription factor FOXO1Insulin sensitivityNormal suppressionClinical significanceReceptor substrate-1Adipose tissueExpression of Fst
2009
The Irs1 Branch of the Insulin Signaling Cascade Plays a Dominant Role in Hepatic Nutrient Homeostasis
Guo S, Copps K, Dong X, Park S, Cheng Z, Pocai A, Rossetti L, Sajan M, Farese R, White M. The Irs1 Branch of the Insulin Signaling Cascade Plays a Dominant Role in Hepatic Nutrient Homeostasis. Molecular And Cellular Biology 2009, 29: 5070-5083. PMID: 19596788, PMCID: PMC2738277, DOI: 10.1128/mcb.00138-09.Peer-Reviewed Original ResearchConceptsHigh-fat dietHepatic nutrient homeostasisIntracerebroventricular insulin infusionSuppression of HGPImpaired glucose toleranceHyperinsulinemic-euglycemic clampHepatic insulin actionHepatic glucose productionHepatic Irs1Cre-loxP approachLivers of controlGlucose toleranceInsulin infusionInsulin Signaling CascadeInsulin sensitivityPostprandial hyperglycemiaGlucose homeostasisInsulin actionPrincipal mediatorGlucose productionLipogenic genesMiceTyrosine phosphorylationLiverIRS2Insulin Receptor Substrate-2 in β-Cells Decreases Diabetes in Nonobese Diabetic Mice
Norquay L, D'Aquino K, Opare-Addo L, Kuznetsova A, Haas M, Bluestone J, White M. Insulin Receptor Substrate-2 in β-Cells Decreases Diabetes in Nonobese Diabetic Mice. Endocrinology 2009, 150: 4531-4540. PMID: 19574401, PMCID: PMC2754683, DOI: 10.1210/en.2009-0395.Peer-Reviewed Original ResearchConceptsNonobese diabetic (NOD) miceBeta-cell destructionNOD miceInsulin receptor substrate 2Glucose toleranceDiabetes incidenceDiabetic miceIslet massAnti-CD3 antibody injectionNondiabetic NOD miceReduced diabetes incidenceRisk of diabetesBeta-cell massType 1 diabetesBetter glucose toleranceAnti-CD3 antibodyBeta-cell growthWk of ageDiabetic NODSevere insulitisOvert diabetesSubstrate 2C57BL/6 miceBeta-cell mitogenesisAntibody injection
2005
Cyclins D2 and D1 Are Essential for Postnatal Pancreatic β-Cell Growth
Kushner J, Ciemerych M, Sicinska E, Wartschow L, Teta M, Long S, Sicinski P, White M. Cyclins D2 and D1 Are Essential for Postnatal Pancreatic β-Cell Growth. Molecular And Cellular Biology 2005, 25: 3752-3762. PMID: 15831479, PMCID: PMC1084308, DOI: 10.1128/mcb.25.9.3752-3762.2005.Peer-Reviewed Original ResearchConceptsBeta-cell massAdult beta-cell massD2 mRNA expressionCyclin D2 mRNA expressionBeta-cell proliferationMonths of agePancreatic β-cell growthBeta cell expansionΒ-cell growthGlucose intoleranceGlucose toleranceInsulin secretionGlucose homeostasisAdult miceBeta cellsIslet growthPancreatic isletsCyclin D1MRNA expressionDiabetesMiceCyclin D2Cyclin D3Adult murineIslet development
2004
Islet-Sparing Effects of Protein Tyrosine Phosphatase-1b Deficiency Delays Onset of Diabetes in IRS2 Knockout Mice
Kushner J, Haj F, Klaman L, Dow M, Kahn B, Neel B, White M. Islet-Sparing Effects of Protein Tyrosine Phosphatase-1b Deficiency Delays Onset of Diabetes in IRS2 Knockout Mice. Diabetes 2004, 53: 61-66. PMID: 14693698, DOI: 10.2337/diabetes.53.1.61.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseCrosses, GeneticDiabetes Mellitus, Type 1Glucose Tolerance TestInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsIslets of LangerhansKineticsLeptinMaleMiceMice, KnockoutModels, AnimalPhosphoproteinsProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine PhosphatasesSignal TransductionConceptsPeripheral insulin sensitivityBeta-cell areaBeta-cell functionInsulin sensitivityPancreatic beta cell areaPancreatic beta-cell functionDecreased insulin requirementIrs2 knockout miceBeta cell homeostasisMonths of ageInsulin requirementsPeripheral actionsGlucose toleranceGlucose homeostasisKnockout miceDelay onsetMiceInsulin receptorPTP1B deficiencyDiabetesReceptor complexIRS2Novel roleInsulinDownstream targets
2002
Defective insulin secretion in pancreatic β cells lacking type 1 IGF receptor
Xuan S, Kitamura T, Nakae J, Politi K, Kido Y, Fisher P, Morroni M, Cinti S, White M, Herrera P, Accili D, Efstratiadis A. Defective insulin secretion in pancreatic β cells lacking type 1 IGF receptor. Journal Of Clinical Investigation 2002, 110: 1011-1019. PMID: 12370279, PMCID: PMC151144, DOI: 10.1172/jci15276.Peer-Reviewed Original ResearchConceptsType 1 IGF receptorBeta-cell massDefective insulin secretionInsulin secretionIGF receptorInsulin releaseInadequate compensatory increaseGlucose-dependent insulin releaseBeta-cell proliferationAge-dependent impairmentPancreatic β-cellsGlucose toleranceDecrease of glucoseBeta cellsType 2Compensatory increaseCell massΒ-cellsReceptor tyrosine kinasesSecretionCell proliferationAntiapoptotic roleReceptorsTyrosine kinaseConditional mutagenesisPdx1 restores β cell function in Irs2 knockout mice
Kushner J, Ye J, Schubert M, Burks D, Dow M, Flint C, Dutta S, Wright C, Montminy M, White M. Pdx1 restores β cell function in Irs2 knockout mice. Journal Of Clinical Investigation 2002, 109: 1193-1201. PMID: 11994408, PMCID: PMC150960, DOI: 10.1172/jci14439.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBlood GlucoseBody WeightDiabetes Mellitus, Type 2FemaleHomeodomain ProteinsInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsIslets of LangerhansMaleMiceMice, KnockoutPhosphoproteinsReceptor, InsulinSignal TransductionTrans-ActivatorsConceptsOnset of diabetesPeripheral insulin actionBeta-cell failureType 2 diabetesBeta-cell massEarly-onset diabetesIrs2 knockout micePancreatic beta-cell growthBeta-cell growthWeeks of ageIrs2 branchHepatocyte nuclear factorGlucose toleranceExpression of Pdx1Knockout miceBeta cellsDiabetesInsulin actionInsulin/MiceNuclear factorTranscription factor Pdx1Cell functionIsletsTransgenic expression