2022
Hyperinsulinemia induces early and dyssynchronous puberty in lean female mice.
Saleh FL, Joshi AA, Tal A, Xu P, Hens J, Wong SL, Flannery C. Hyperinsulinemia induces early and dyssynchronous puberty in lean female mice. Journal Of Endocrinology 2022, 254: 121-135. PMID: 35904489, PMCID: PMC9837806, DOI: 10.1530/joe-21-0447.Peer-Reviewed Original ResearchConceptsVaginal openingInsulin resistanceDay of VOIGF-1 levelsInsulin-like growth factor 1 receptorGreater insulin resistanceHigher insulin levelsEffect of hyperinsulinemiaGrowth factor 1 receptorGonadotropin-releasing hormoneLower body weightFactor 1 receptorReceptor isoform expressionMammary gland developmentLH levelsInsulin levelsInsulin receptor isoform expressionKisspeptin expressionChildhood obesityFemale miceHormone levelsEarly initiationHyperinsulinemiaBody weightOvarian follicles
2018
Insulin Regulates Glycogen Synthesis in Human Endometrial Glands Through Increased GYS2
Flannery CA, Choe GH, Cooke KM, Fleming AG, Radford CC, Kodaman PH, Jurczak MJ, Kibbey RG, Taylor HS. Insulin Regulates Glycogen Synthesis in Human Endometrial Glands Through Increased GYS2. The Journal Of Clinical Endocrinology & Metabolism 2018, 103: 2843-2850. PMID: 29726999, PMCID: PMC6276707, DOI: 10.1210/jc.2017-01759.Peer-Reviewed Original ResearchConceptsGlucose metabolismGlycogen synthesisSecretory phase endometriumEndometrial epithelial cellsHuman endometrial glandsGlycogen synthase kinase 3α/βSynthase kinase 3α/βMaternal obesityHealthy womenEndometrial glandsEarly pregnancyHuman endometriumGSK3α/βOutcome measurementsSuccessful implantationFetal developmentEndometriumCritical metabolic functionsInsulinGlycogen contentProgesteroneSustain embryo developmentEpithelial cellsInsulin receptorPotential role
2017
Ovarian Morphology by Transabdominal Ultrasound Correlates With Reproductive and Metabolic Disturbance in Adolescents With PCOS
Rackow BW, Brink H, Hammers L, Flannery CA, Lujan ME, Burgert TS. Ovarian Morphology by Transabdominal Ultrasound Correlates With Reproductive and Metabolic Disturbance in Adolescents With PCOS. Journal Of Adolescent Health 2017, 62: 288-293. PMID: 29217212, PMCID: PMC9843701, DOI: 10.1016/j.jadohealth.2017.09.005.Peer-Reviewed Original ResearchConceptsPolycystic ovary syndromeOvarian volumeOvarian areaOvarian morphologyTotal testosteroneFree testosteroneTransabdominal ultrasonographyFollicle distribution patternBody mass indexRetrospective pilot studyRank correlation coefficientOvary syndromeHormonal testsIndependent predictorsMass indexUltrasound correlatesPhysical examinationFollicle numberMenstrual cycleMetabolic disturbancesHormone ratioMetabolic dysfunctionSonographic featuresReproductive dysfunctionGlucose levelsTime course analysis of RNA quality in placenta preserved by RNAlater or flash freezing
Martin NM, Cooke KM, Radford CC, Perley LE, Silasi M, Flannery CA. Time course analysis of RNA quality in placenta preserved by RNAlater or flash freezing. American Journal Of Reproductive Immunology 2017, 77 PMID: 28138995, PMCID: PMC5397349, DOI: 10.1111/aji.12637.Peer-Reviewed Original Research
2016
Endometrial Cancer-Associated FGF18 Expression Is Reduced by Bazedoxifene in Human Endometrial Stromal Cells In Vitro and in Murine Endometrium
Flannery CA, Fleming AG, Choe GH, Naqvi H, Zhang M, Sharma A, Taylor HS. Endometrial Cancer-Associated FGF18 Expression Is Reduced by Bazedoxifene in Human Endometrial Stromal Cells In Vitro and in Murine Endometrium. Endocrinology 2016, 157: 3699-3708. PMID: 27267714, PMCID: PMC5045514, DOI: 10.1210/en.2016-1233.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsBasic Helix-Loop-Helix Transcription FactorsCarcinoma, EndometrioidCase-Control StudiesCells, CulturedEndometrial HyperplasiaEndometrial NeoplasmsEndometriumFemaleFibroblast Growth FactorsGene Expression ProfilingHumansIndolesMiceMiddle AgedSelective Estrogen Receptor ModulatorsConceptsStromal cellsPostmenopausal womenHormone therapyEpithelial proliferationFGF18 expressionAntiproliferative effectsSelective estrogen receptor modulatorsHuman endometrial stromal cellsGrowth factorBZA/CEMenopausal hormone therapyEndometrial stromal cellsBreast cancer riskEstrogen receptor modulatorsCD1 female miceE74-like factor 5Normal proliferative endometriumParacrine growth factorPrimary stromal cellsTyrosine kinase receptor 2Fibroblast growth factorEndometrial hyperplasiaEndometrial proliferationEndometrial cancerEndometrial adenocarcinomaDifferential Expression of IR-A, IR-B and IGF-1R in Endometrial Physiology and Distinct Signature in Adenocarcinoma
Flannery CA, Saleh FL, Choe GH, Selen DJ, Kodaman PH, Kliman HJ, Wood TL, Taylor HS. Differential Expression of IR-A, IR-B and IGF-1R in Endometrial Physiology and Distinct Signature in Adenocarcinoma. The Journal Of Clinical Endocrinology & Metabolism 2016, 101: 2883-2891. PMID: 27088794, PMCID: PMC4929835, DOI: 10.1210/jc.2016-1795.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAntigens, CDCarcinoma, EndometrioidCells, CulturedEndometrial HyperplasiaEndometrial NeoplasmsEndometriumFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMenstrual CycleMiddle AgedProtein SubunitsReceptor, IGF Type 1Receptor, InsulinTranscriptomeConceptsIGF-1R expressionEndometrial hyperplasiaNormal endometriumEndometrial physiologySecretory phaseProliferative phaseIGF-1 receptor mRNAIR-B expressionNormal secretory phaseType 2 diabetesSex steroid treatmentEarly secretory phaseEarly proliferative phaseNormal proliferative phaseEndometrial proliferationEndometrioid adenocarcinomaComplex hyperplasiaEndometrial adenocarcinomaMass indexMenstrual cycleRisk factorsReceptor expressionIGF-1RMAIN OUTCOMEReceptor mRNADevelopment of a Quantitative PCR Assay for Detection of Human Insulin-Like Growth Factor Receptor and Insulin Receptor Isoforms
Flannery CA, Rowzee AM, Choe GH, Saleh FL, Radford CC, Taylor HS, Wood TL. Development of a Quantitative PCR Assay for Detection of Human Insulin-Like Growth Factor Receptor and Insulin Receptor Isoforms. Endocrinology 2016, 157: 1702-1708. PMID: 26862994, PMCID: PMC4816738, DOI: 10.1210/en.2015-1698.Peer-Reviewed Original ResearchConceptsSplice variantsInsulin-like growth factor (IGF) ligandsInsulin-like growth factor receptorGrowth factor ligandsSpecific molecular signaturesQuantitative PCR assaysGrowth factor receptorHigh homologyMRNA sequencesQuantitative RT-PCRIGF-1 receptorFactor ligandInsulin receptor isoformsCompetition assaysPrimer pairsRelative abundanceInsulin receptorMolecular signaturesCell typesDifferent tissuesIGF-1R mRNAFactor receptorExpression levelsGel electrophoresisReceptor isoforms
2015
H19 lncRNA alters stromal cell growth via IGF signaling in the endometrium of women with endometriosis
Ghazal S, McKinnon B, Zhou J, Mueller M, Men Y, Yang L, Mueller M, Flannery C, Huang Y, Taylor HS. H19 lncRNA alters stromal cell growth via IGF signaling in the endometrium of women with endometriosis. EMBO Molecular Medicine 2015, 7: 996-1003. PMID: 26089099, PMCID: PMC4551339, DOI: 10.15252/emmm.201505245.Peer-Reviewed Original ResearchConceptsChronic pelvic painReproductive-aged womenEndometrium of womenEndometrial stromal cellsStromal cell growthEndometrial preparationPelvic painEutopic endometriumAged womenEndometriosisNormal controlsStromal cellsH19 expressionImpact fertilityMolecular spongeH19/letNovel therapeuticsReduced proliferationInfertilityWomenEndometriumTurn inhibitsMicroRNA let-7Molecular mechanismsCell growth
2014
mRNA-Binding Protein TIA-1 Reduces Cytokine Expression in Human Endometrial Stromal Cells and Is Down-Regulated in Ectopic Endometrium
Karalok HM, Aydin E, Saglam O, Torun A, Guzeloglu-Kayisli O, Lalioti MD, Kristiansson H, Duke CM, Choe G, Flannery C, Kallen CB, Seli E. mRNA-Binding Protein TIA-1 Reduces Cytokine Expression in Human Endometrial Stromal Cells and Is Down-Regulated in Ectopic Endometrium. The Journal Of Clinical Endocrinology & Metabolism 2014, 99: e2610-e2619. PMID: 25140393, PMCID: PMC4255110, DOI: 10.1210/jc.2013-3488.Peer-Reviewed Original ResearchConceptsHuman endometrial stromal cellsTNF-α expressionTIA-1 expressionEndometrial stromal cellsIL-6Pathogenesis of endometriosisMenstrual cycleTIA-1Endometrial tissueEctopic endometriumImmune factorsHistological scoresCultured human endometrial stromal cellsSteroid hormonesStromal cellsGrowth factorElevated IL-6Ectopic endometrial tissueNormal menstrual cycleEutopic endometrial tissuesGrowth factor expressionT-cell intracellular antigenEndometrial cytokinesEndometrial functionControl womenThe H19/let-7 double-negative feedback loop contributes to glucose metabolism in muscle cells
Gao Y, Wu F, Zhou J, Yan L, Jurczak MJ, Lee HY, Yang L, Mueller M, Zhou XB, Dandolo L, Szendroedi J, Roden M, Flannery C, Taylor H, Carmichael GG, Shulman GI, Huang Y. The H19/let-7 double-negative feedback loop contributes to glucose metabolism in muscle cells. Nucleic Acids Research 2014, 42: 13799-13811. PMID: 25399420, PMCID: PMC4267628, DOI: 10.1093/nar/gku1160.Peer-Reviewed Original ResearchConceptsDouble-negative feedback loopLet-7PI3K/Akt-dependent phosphorylationLet-7 targetsHuman genetic disordersAkt-dependent phosphorylationMuscle cellsInsulin-resistant rodentsSponge lncRNAsMolecular spongeH19 lncRNAFeedback loopGrowth controlDepletion resultsH19Impaired insulinLncRNAsTarget miRNAGlucose uptakeGenetic disordersBiogenesisCellsKSRPPhosphorylationMicroRNAsGlucose and Metformin Modulate Human First Trimester Trophoblast Function: a Model and Potential Therapy for Diabetes‐Associated Uteroplacental Insufficiency
Han CS, Herrin MA, Pitruzzello MC, Mulla MJ, Werner EF, Pettker CM, Flannery CA, Abrahams VM. Glucose and Metformin Modulate Human First Trimester Trophoblast Function: a Model and Potential Therapy for Diabetes‐Associated Uteroplacental Insufficiency. American Journal Of Reproductive Immunology 2014, 73: 362-371. PMID: 25394884, PMCID: PMC4356646, DOI: 10.1111/aji.12339.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis Inducing AgentsAntigens, CDCarrier ProteinsCell LineCell MovementChemokine CCL5Chemokine CXCL1Diabetes ComplicationsDiabetes MellitusEndoglinFemaleGlucoseGranulocyte Colony-Stimulating FactorHumansInflammationInterleukinsMetforminNLR Family, Pyrin Domain-Containing 3 ProteinPlacentaPre-EclampsiaPregnancyPregnancy Trimester, FirstReceptors, Cell SurfaceTrophoblastsUterusVascular Endothelial Growth Factor Receptor-1ConceptsHuman first trimester trophoblast cell lineAnti-angiogenic factor sFlt-1First trimester trophoblast cell lineNalp3/ASC inflammasomeInflammatory cytokines/chemokinesFirst trimester trophoblast cellsGlucose-induced inflammationRisk of preeclampsiaCytokines/chemokinesAbsence of metforminIL-1β productionIL-1β secretionTrophoblast cell lineUteroplacental insufficiencyIL-1βIL-6SFlt-1Trophoblast functionsIL-8Pathogenic roleInflammatory responseASC inflammasomeSupernatant cytokinesPotential therapyExcess glucose
2012
Skeletal Muscle Insulin Resistance Promotes Increased Hepatic De Novo Lipogenesis, Hyperlipidemia, and Hepatic Steatosis in the Elderly
Flannery C, Dufour S, Rabøl R, Shulman GI, Petersen KF. Skeletal Muscle Insulin Resistance Promotes Increased Hepatic De Novo Lipogenesis, Hyperlipidemia, and Hepatic Steatosis in the Elderly. Diabetes 2012, 61: 2711-2717. PMID: 22829450, PMCID: PMC3478531, DOI: 10.2337/db12-0206.Peer-Reviewed Original ResearchConceptsHepatic de novo lipogenesisNonalcoholic fatty liver diseaseDe novo lipogenesisMuscle insulin resistanceInsulin resistanceElderly subjectsNovo lipogenesisYoung subjectsInsulin resistance promotesSedentary elderly subjectsFatty liver diseaseHigh-carbohydrate mealHepatic triglyceride contentType 2 diabetesMuscle glycogen synthesisGlycogen synthesisLiver glycogen synthesisLiver diseaseNormal weightHepatic steatosisPostprandial changesPlasma TGLiver glycogenHyperlipidemiaMuscle glycogenPolycystic ovary syndrome in adolescence: impaired glucose tolerance occurs across the spectrum of BMI
Flannery CA, Rackow B, Cong X, Duran E, Selen DJ, Burgert TS. Polycystic ovary syndrome in adolescence: impaired glucose tolerance occurs across the spectrum of BMI. Pediatric Diabetes 2012, 14: 42-49. PMID: 22925367, PMCID: PMC4864958, DOI: 10.1111/j.1399-5448.2012.00902.x.Peer-Reviewed Original ResearchConceptsOral glucose tolerance testingPolycystic ovary syndromeAbnormal glucose metabolismGlucose metabolismOB cohortOvary syndromeGlucose toleranceAndrogen Excess Society criteriaHomeostatic model assessmentPresence of obesityGlucose tolerance testingC-reactive proteinType 2 diabetesNon-obese adolescentsHigh-density lipoproteinInsulin levelsInsulin resistanceSubgroup analysisChronic conditionsMetabolic manifestationsReproductive yearsSociety criteriaLipid profileTolerance testingTestosterone levels
2011
Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals
Rabøl R, Petersen KF, Dufour S, Flannery C, Shulman GI. Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 13705-13709. PMID: 21808028, PMCID: PMC3158147, DOI: 10.1073/pnas.1110105108.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseHepatic de novo lipogenesisMuscle insulin resistanceInsulin-resistant individualsDe novo lipogenesisSkeletal muscle insulin resistanceCarbohydrate-rich mealInsulin resistanceHepatic triglyceride synthesisNovo lipogenesisAtherogenic dyslipidemiaMetabolic syndromeRandomized cross-over trialTriglyceride synthesisFatty liver diseasePostprandial plasma glucoseMuscle insulin responsivenessCross-over trialEarly therapeutic targetType 2 diabetesMuscle glycogen synthesisBody energy storageLiver diseasePlasma glucoseSingle bout