2023
Weight Loss-Independent Effect of Liraglutide on Insulin Sensitivity in Individuals With Obesity and Prediabetes.
Mashayekhi M, Nian H, Mayfield D, Devin J, Gamboa J, Yu C, Silver H, Niswender K, Luther J, Brown N. Weight Loss-Independent Effect of Liraglutide on Insulin Sensitivity in Individuals With Obesity and Prediabetes. Diabetes 2023, 73: 38-50. PMID: 37874653, PMCID: PMC10784656, DOI: 10.2337/db23-0356.Peer-Reviewed Original ResearchConceptsEndogenous GLP-1Glucagon-like peptide-1 receptor agonistsPeptide-1 receptor agonistsImproved insulin sensitivityInsulin sensitivityGLP-1GLP-1RGlucagon levelsGlucose levelsMatsuda indexWeight lossHypocaloric dietPostprandial glucoseInhibitor sitagliptinReceptor agonistMetabolic effectsDiet-induced weight lossDipeptidyl peptidase-4 inhibitor sitagliptinGLP-1R agonist liraglutideWeight loss-independent effectsDPP-4 inhibitor sitagliptinDipeptidyl peptidase-4 inhibitionPeptidase-4 inhibitionMixed meal testGLP-1R antagonist
2022
Comparative effects of weight loss and incretin‐based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial
Mashayekhi M, Beckman JA, Nian H, Garner EM, Mayfield D, Devin JK, Koethe JR, Brown JD, Cahill KN, Yu C, Silver H, Niswender K, Luther JM, Brown NJ. Comparative effects of weight loss and incretin‐based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial. Diabetes Obesity And Metabolism 2022, 25: 570-580. PMID: 36306151, PMCID: PMC10306232, DOI: 10.1111/dom.14903.Peer-Reviewed Original ResearchConceptsFlow-mediated vasodilationPlasminogen activator inhibitor-1Vascular endothelial functionEndothelial functionInsulin resistanceWeight lossGlucagon-like peptide-1 receptor agonistsBaseline flow-mediated vasodilationDipeptidyl peptidase-4 inhibitor sitagliptinGLP-1R agonist liraglutideWeight loss-independent mechanismsPeptide-1 receptor agonistsBeneficial effectsEndothelial vasodilator functionGreater endothelial dysfunctionIncretin-based therapiesNormal endothelial functionChemoattractant protein-1Chemokine MCP-1Significant weight lossActivator inhibitor-1Effect of treatmentVasodilator functionUrine albuminEndothelial dysfunction
2021
GSK2256294 Decreases sEH (Soluble Epoxide Hydrolase) Activity in Plasma, Muscle, and Adipose and Reduces F2-Isoprostanes but Does Not Alter Insulin Sensitivity in Humans
Luther JM, Ray J, Wei D, Koethe JR, Hannah L, DeMatteo A, Manning R, Terker AS, Peng D, Nian H, Yu C, Mashayekhi M, Gamboa J, Brown NJ. GSK2256294 Decreases sEH (Soluble Epoxide Hydrolase) Activity in Plasma, Muscle, and Adipose and Reduces F2-Isoprostanes but Does Not Alter Insulin Sensitivity in Humans. Hypertension 2021, 78: 1092-1102. PMID: 34455816, PMCID: PMC8429121, DOI: 10.1161/hypertensionaha.121.17659.Peer-Reviewed Original Research
2018
The Vasculature in Prediabetes
Wasserman DH, Wang TJ, Brown NJ. The Vasculature in Prediabetes. Circulation Research 2018, 122: 1135-1150. PMID: 29650631, PMCID: PMC5901903, DOI: 10.1161/circresaha.118.311912.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme InhibitorsAnimalsBlood VesselsCardiovascular DiseasesCombined Modality TherapyDiabetes Mellitus, Type 2Diet, ReducingDisease ProgressionEndothelium, VascularExtracellular MatrixFatty Acids, NonesterifiedFibrinolysisGlucoseHumansHyperglycemiaHypoglycemic AgentsInflammationInsulin ResistanceLife StyleMetabolic SyndromeMiceMicrocirculationMicroRNAsMuscle, SkeletalObesityPrediabetic StateRiskWeight LossConceptsFrequency of prediabetesMainstay of treatmentPrevalence of obesityConcomitant obesityEndothelial dysfunctionExtracellular matrix remodelingDiabetes mellitusEndothelial functionRenal diseaseMetabolic derangementsFibrinolytic dysfunctionEndothelial vasodilatorsInsulin resistanceInsulin sensitivityCardiovascular diseaseDelivery of insulinSlow progressionPrediabetesWeight lossSkeletal muscleMatrix remodelingMellitusObesityDysfunctionDisease
2016
Epoxyeicosatrienoic acids and glucose homeostasis in mice and men
Luther JM, Brown NJ. Epoxyeicosatrienoic acids and glucose homeostasis in mice and men. Prostaglandins And Other Lipid Mediators 2016, 125: 2-7. PMID: 27448715, PMCID: PMC5035218, DOI: 10.1016/j.prostaglandins.2016.07.010.Peer-Reviewed Original ResearchMeSH Keywords8,11,14-Eicosatrienoic AcidAnimalsDiabetes Mellitus, Type 2GlucoseHomeostasisHumansInsulin ResistanceMiceSignal TransductionConceptsEpoxyeicosatrienoic acidsInsulin sensitivityRodent modelsSoluble epoxide hydrolaseGlucose homeostasisEpoxide hydrolaseActive dihydroxyeicosatrienoic acidsPancreatic islet cell functionEffects of EETsType 2 diabetesType 1 diabetesIslet cell functionP450 epoxygenasesDihydroxyeicosatrienoic acidsPeripheral tissuesIslet cellsPharmacological inhibitionArachidonic acidDiabetesCell functionGenetic polymorphismsFavorable effectTissue expressionStable analogueCompelling evidence
2015
Treatment with Sildenafil Improves Insulin Sensitivity in Prediabetes: A Randomized, Controlled Trial
Ramirez CE, Nian H, Yu C, Gamboa JL, Luther JM, Brown NJ, Shibao CA. Treatment with Sildenafil Improves Insulin Sensitivity in Prediabetes: A Randomized, Controlled Trial. The Journal Of Clinical Endocrinology & Metabolism 2015, 100: 4533-4540. PMID: 26580240, PMCID: PMC4667163, DOI: 10.1210/jc.2015-3415.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlbuminuriaDouble-Blind MethodEndothelium, VascularFemaleFibrinolysisGlucoseGlucose Clamp TechniqueGlucose Tolerance TestHemodynamicsHumansInsulinInsulin ResistanceMaleMiddle AgedOverweightPhosphodiesterase 5 InhibitorsPlasminogen Activator Inhibitor 1Prediabetic StateSildenafil CitrateConceptsPhosphodiesterase-5 inhibitionGlucose-stimulated insulin secretionInsulin sensitivity indexInsulin sensitivityInsulin secretionBaseline insulin sensitivity indexPlacebo-controlled studyClinical Research CenterBody mass indexEnd of treatmentPlasminogen activator inhibitor-1Tissue plasminogen activatorActivator inhibitor-1Placebo groupUrine albuminSildenafil groupCreatinine ratioEndothelial functionPrimary outcomeMass indexTreatment armsFibrinolytic balanceDisposition indexHyperglycemic clampOverweight individuals
2014
Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans
Ramirez CE, Shuey MM, Milne GL, Gilbert K, Hui N, Yu C, Luther JM, Brown NJ. Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans. Prostaglandins And Other Lipid Mediators 2014, 113: 38-44. PMID: 25173047, PMCID: PMC4253976, DOI: 10.1016/j.prostaglandins.2014.08.001.Peer-Reviewed Original ResearchConceptsInsulin sensitivity indexEpoxyeicosatrienoic acidsInsulin sensitivityHigher insulin sensitivity indexPlasma epoxyeicosatrienoic acidsGlucose-stimulated insulin secretionBody mass indexArg/ArgSoluble epoxide hydrolase activitySoluble epoxide hydrolaseMetabolic syndromeMass indexDisposition indexInsulin resistanceHyperglycemic clampInsulin secretionSensitivity indexEpoxide hydrolase activityEPHX2Hydrolase activitySecretionPhenotyping studiesMetabolic phenotyping studiesEpoxide hydrolaseGenetic variantsDietary Sodium Restriction Decreases Insulin Secretion Without Affecting Insulin Sensitivity in Humans
Luther JM, Byrne LM, Yu C, Wang TJ, Brown NJ. Dietary Sodium Restriction Decreases Insulin Secretion Without Affecting Insulin Sensitivity in Humans. The Journal Of Clinical Endocrinology & Metabolism 2014, 99: e1895-e1902. PMID: 25029426, PMCID: PMC4184066, DOI: 10.1210/jc.2014-2122.Peer-Reviewed Original ResearchConceptsHigh sodium dietHigh sodium intakeInsulin sensitivity indexSodium intakeInsulin secretionAldosterone systemAldosterone infusionInsulin sensitivityAcademic clinical research centerAcute insulin secretory responseLow dietary sodium intakeDecrease insulin secretionC-peptide responsePlasma renin activityDietary sodium intakeLow sodium dietSystolic blood pressureClinical Research CenterInsulin secretory responseAcute insulin responseHigh-risk individualsImpairs insulin secretionGlucose-stimulated insulinIncident diabetesNormotensive volunteers
2012
Differential Effects of Nebivolol and Metoprolol on Insulin Sensitivity and Plasminogen Activator Inhibitor in the Metabolic Syndrome
Ayers K, Byrne LM, DeMatteo A, Brown NJ. Differential Effects of Nebivolol and Metoprolol on Insulin Sensitivity and Plasminogen Activator Inhibitor in the Metabolic Syndrome. Hypertension 2012, 59: 893-898. PMID: 22353614, PMCID: PMC3402551, DOI: 10.1161/hypertensionaha.111.189589.Peer-Reviewed Original ResearchConceptsEffects of nebivololMetabolic syndromeBlood pressureInsulin sensitivityPlasminogen activator inhibitorAntagonist metoprololGlucose homeostasisThird-generation β-blockerActivator inhibitorMarkers of fibrinolysisCongestive heart failureDiastolic blood pressureLower blood pressureSystolic blood pressureCoronary artery diseaseGlucose tolerance testLarge clinical trialsDetrimental metabolic effectsPlasminogen activator inhibitor-1Insulin sensitivity indexAcute insulin responseΒ-cell functionActivator inhibitor-1Study drugArtery disease
2011
The renin–angiotensin–aldosterone system and glucose homeostasis
Luther JM, Brown NJ. The renin–angiotensin–aldosterone system and glucose homeostasis. Trends In Pharmacological Sciences 2011, 32: 734-739. PMID: 21880378, PMCID: PMC3223326, DOI: 10.1016/j.tips.2011.07.006.Peer-Reviewed Original ResearchConceptsAldosterone systemΒ-cellsGlucose-stimulated insulin secretionIncidence of diabetesLarge clinical trialsInduces Insulin ResistanceCultured β-cellsPancreatic β-cellsRAAS inhibitionAng IIAngiotensin IIInsulin resistanceHeart diseaseClinical trialsDiabetes progressionMineralocorticoid receptorPharmacological strategiesInsulin secretionGlucose homeostasisPancreatic isletsOxidative stressDiabetesIndependent mechanismsGlucose transportCellular level
2010
Low-salt diet increases insulin resistance in healthy subjects
Garg R, Williams GH, Hurwitz S, Brown NJ, Hopkins PN, Adler GK. Low-salt diet increases insulin resistance in healthy subjects. Metabolism 2010, 60: 965-968. PMID: 21036373, PMCID: PMC3036792, DOI: 10.1016/j.metabol.2010.09.005.Peer-Reviewed Original ResearchConceptsLow-salt dietHomeostasis model assessment indexModel assessment indexBody mass indexInsulin resistanceLS dietUrine aldosteroneMass indexHS dietHealthy subjectsHigher homeostasis model assessment indexUrine norepinephrine excretionPlasma renin activityHigh-salt dietSympathetic nervous systemSerum angiotensin IIPathogenesis of diabetesUrine epinephrineNorepinephrine excretionRenin activitySerum aldosteroneBlood pressureSerum sodiumAngiotensin IIHealthy men
2008
The T8590C Polymorphism of CYP4A11 and 20-Hydroxyeicosatetraenoic Acid in Essential Hypertension
Laffer CL, Gainer JV, Waterman MR, Capdevila JH, Laniado-Schwartzman M, Nasjletti A, Brown NJ, Elijovich F. The T8590C Polymorphism of CYP4A11 and 20-Hydroxyeicosatetraenoic Acid in Essential Hypertension. Hypertension 2008, 51: 767-772. PMID: 18227405, PMCID: PMC2365894, DOI: 10.1161/hypertensionaha.107.102921.Peer-Reviewed Original ResearchConceptsBlood pressureC carriersHypertensive subjectsSalt-sensitive hypertensive subjectsHigher diastolic blood pressureT8590C polymorphismSalt-sensitive subjectsDiastolic blood pressureMicroU/mLDahl S ratsSerum insulin concentrationsC allele carriersC allele frequencySalt sensitivityPressure natriuresisEssential hypertensionFractional excretionSerum insulinHip ratioHuman hypertensionInsulin resistanceInsulin sensitivitySodium balanceInsulin concentrationsTT subjects
2004
Prevention of Obesity and Insulin Resistance in Mice Lacking Plasminogen Activator Inhibitor 1
Ma LJ, Mao SL, Taylor KL, Kanjanabuch T, Guan Y, Zhang Y, Brown NJ, Swift LL, McGuinness OP, Wasserman DH, Vaughan DE, Fogo AB. Prevention of Obesity and Insulin Resistance in Mice Lacking Plasminogen Activator Inhibitor 1. Diabetes 2004, 53: 336-346. PMID: 14747283, DOI: 10.2337/diabetes.53.2.336.Peer-Reviewed Original ResearchMeSH KeywordsAdiponectinAnimalsBlood GlucoseCalorimetry, IndirectCarrier ProteinsDisease Models, AnimalGlucose Clamp TechniqueHyperinsulinismInsulinInsulin ResistanceIntercellular Signaling Peptides and ProteinsIon ChannelsMaleMembrane ProteinsMiceMice, KnockoutMitochondrial ProteinsObesityPlasminogen Activator Inhibitor 1Polymerase Chain ReactionProteinsRNA, MessengerTranscription, GeneticTriglyceridesUncoupling Protein 1Weight GainConceptsPlasminogen activator inhibitor-1Prevention of obesityInsulin resistanceHF dietWT miceActivator inhibitor-1Insulin sensitivityPAI-1Angiotensin type 1 receptor antagonistType 1 receptor antagonistDiet-induced obesity modelEuglycemic hyperinsulinemic clamp studyProtein-3 mRNA expressionInhibitor-1PAI-1-deficient micePeroxisome proliferator-activated receptorDiet-induced obesityPAI-1 levelsPAI-1 deficiencyPAI-1 increaseWhite adipose tissueProliferator-activated receptorInsulin-stimulated glucose uptakeTotal energy expenditureDirect causal role
2002
ACE Inhibition Versus Angiotensin Type 1 Receptor Antagonism
Brown NJ, Kumar S, Painter CA, Vaughan DE. ACE Inhibition Versus Angiotensin Type 1 Receptor Antagonism. Hypertension 2002, 40: 859-865. PMID: 12468570, DOI: 10.1161/01.hyp.0000040264.15961.48.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsAntihypertensive AgentsBlood GlucoseBlood PressureDiureticsDose-Response Relationship, DrugDrug Therapy, CombinationFemaleHumansHydrochlorothiazideHypertensionInsulinInsulin ResistanceLosartanMaleMiddle AgedPlasminogen Activator Inhibitor 1RamiprilReceptor, Angiotensin, Type 1Renin-Angiotensin SystemSodium Chloride Symporter InhibitorsTissue Plasminogen ActivatorTreatment OutcomeConceptsPlasminogen activator inhibitor-1PAI-1 antigenAngiotensin type 1 receptor antagonismPlasma PAI-1 antigenAT1 receptor antagonismReceptor antagonismACE inhibitionAddition of ramiprilAngiotensin receptor antagonismWeeks of hydrochlorothiazideEffects of losartanPlasma PAI-1Activator inhibitor-1Aldosterone systemHypertensive subjectsBlood pressureFibrinolytic variablesMyocardial infarctionTPA antigenRisk factorsTreatment periodLosartanTPA activityAntigenInhibitor-1PAI-1 in human hypertension: relation to hypertensive groups*
Srikumar N, Brown NJ, Hopkins PN, Jeunemaitre X, Hunt SC, Vaughan DE, Williams GH. PAI-1 in human hypertension: relation to hypertensive groups*. American Journal Of Hypertension 2002, 15: 683-690. PMID: 12160190, DOI: 10.1016/s0895-7061(02)02952-7.Peer-Reviewed Original ResearchConceptsPlasma renin activityPAI-1 levelsPlasminogen activator inhibitor type 1Hypertensive subjectsInsulin resistanceLow reninRenin activityHigher PAI-1 levelsDietary salt restrictionLow-salt dietRenin-angiotensin systemActivator inhibitor type 1Inhibitor type 1Aldosterone levelsHypertensive groupSalt restrictionSodium dietSodium restrictionSalt dietHuman hypertensionType 1AldoModulator groupsNonmodulatorsRenin