2016
Risk for Hospitalized Heart Failure Among New Users of Saxagliptin, Sitagliptin, and Other Antihyperglycemic Drugs: A Retrospective Cohort Study.
Toh S, Hampp C, Reichman ME, Graham DJ, Balakrishnan S, Pucino F, Hamilton J, Lendle S, Iyer A, Rucker M, Pimentel M, Nathwani N, Griffin MR, Brown NJ, Fireman BH. Risk for Hospitalized Heart Failure Among New Users of Saxagliptin, Sitagliptin, and Other Antihyperglycemic Drugs: A Retrospective Cohort Study. Annals Of Internal Medicine 2016, 164: 705-14. PMID: 27110660, PMCID: PMC5178978, DOI: 10.7326/m15-2568.Peer-Reviewed Original ResearchConceptsHospitalized heart failureMini-Sentinel programCohort studyHeart failureAntihyperglycemic agentsPropensity score-matched analysisDipeptidyl peptidase-4 inhibitorsNew-user cohort studyU.S. FoodPrior cardiovascular diseaseRetrospective cohort studyPeptidase-4 inhibitorsSubgroup of patientsPrincipal discharge diagnosisDPP-4 inhibitorsSecond-generation sulfonylureasType 2 diabetesLarge cohort studyDisease risk scoreSitagliptin usersStudy drugHazard ratioDischarge diagnosisNinth RevisionResidual confounding
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
Cardiovascular effects of antidiabetic agents: focus on blood pressure effects of incretin-based therapies
Brown NJ. Cardiovascular effects of antidiabetic agents: focus on blood pressure effects of incretin-based therapies. International Journal Of Cardiology Cardiovascular Risk And Prevention 2012, 6: 163-168. PMID: 22433315, PMCID: PMC3422131, DOI: 10.1016/j.jash.2012.02.003.Peer-Reviewed Original ResearchConceptsGlucagon-like peptide-1Cardiovascular eventsDipeptidyl peptidase IV inhibitorsAntidiabetic agentsPeptidase IV inhibitorsBlood pressureClinical trialsPeptide-1Animal modelsType 2 diabetes mellitusIncretin-based agentsBlood pressure effectsIncretin-based therapiesIV inhibitorsLarge clinical trialsFavorable effectIschemia/reperfusionTight glucose controlOverweight diabeticsCardiovascular effectsCardiovascular riskDiabetes mellitusIntensive therapyGlucose controlThiazolidinedione rosiglitazone
2011
Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets
Luther JM, Luo P, Kreger MT, Brissova M, Dai C, Whitfield TT, Kim HS, Wasserman DH, Powers AC, Brown NJ. Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets. Diabetologia 2011, 54: 2152-2163. PMID: 21519965, PMCID: PMC3216479, DOI: 10.1007/s00125-011-2158-9.Peer-Reviewed Original ResearchConceptsWild-type miceGlucose-stimulated insulin secretionHigh sodium intakeEffects of aldosteroneInsulin secretionSodium intakeHyperglycaemic clampInsulin sensitivityEuglycaemic–hyperinsulinaemic clamp studiesSuperoxide dismutase mimetic tempolRelative aldosterone excessMineralocorticoid receptor antagonismDismutase mimetic tempolMineralocorticoid receptor antagonistsC-peptide concentrationsOnset of diabetesConclusions/interpretationWeMIN6 beta-cell lineBeta-cell lineAldosterone excessRenin activityGlucose intoleranceAldosterone deficiencyAngiotensin IIReceptor antagonism
2010
Interactive Hemodynamic Effects of Dipeptidyl Peptidase-IV Inhibition and Angiotensin-Converting Enzyme Inhibition in Humans
Marney A, Kunchakarra S, Byrne L, Brown NJ. Interactive Hemodynamic Effects of Dipeptidyl Peptidase-IV Inhibition and Angiotensin-Converting Enzyme Inhibition in Humans. Hypertension 2010, 56: 728-733. PMID: 20679179, PMCID: PMC3305047, DOI: 10.1161/hypertensionaha.110.156554.Peer-Reviewed Original ResearchMeSH KeywordsAdultAldosteroneAngiotensin-Converting Enzyme InhibitorsBlood GlucoseBlood PressureDiabetes Mellitus, Type 2Dipeptidyl Peptidase 4Dose-Response Relationship, DrugDouble-Blind MethodDrug InteractionsDrug Therapy, CombinationEnalaprilFemaleHeart RateHemodynamicsHumansInsulinMaleMetabolic SyndromeMiddle AgedPeptidyl-Dipeptidase AProspective StudiesPyrazinesRenal CirculationSitagliptin PhosphateSodiumTriazolesConceptsDipeptidyl peptidase IV inhibitionACE inhibitionHypotensive responseHemodynamic effectsBlood pressureHeart rateSerum dipeptidyl peptidase IV activityAngiotensin-Converting Enzyme InhibitionAcute ACE inhibitionVasoconstrictor neuropeptide YBlood pressure responseRenal blood flowSympathetic nervous systemType 2 diabeticsCross-over fashionDipeptidyl peptidase IV inhibitorsDose-dependent effectDipeptidyl peptidase IV activityDose-dependent mannerPeptidase IV inhibitorsPeptidase IV activityMetabolic syndromeNorepinephrine concentrationsIncretin hormonesNeuropeptide Y
2008
Inhaled Insulin Is Associated with Prolonged Enhancement of Glucose Disposal in Muscle and Liver in the Canine
Edgerton DS, Cherrington AD, Neal DW, Scott M, Lautz M, Brown N, Petro J, Hobbs CH, Leach C, Del Parigi A, Strack TR. Inhaled Insulin Is Associated with Prolonged Enhancement of Glucose Disposal in Muscle and Liver in the Canine. Journal Of Pharmacology And Experimental Therapeutics 2008, 328: 970-975. PMID: 19098161, PMCID: PMC3202424, DOI: 10.1124/jpet.108.146985.Peer-Reviewed Original ResearchConceptsInhalation of insulinPlasma glucose levelsGlucose levelsDiabetic patientsGlucose disposalNet hepatic glucose uptakeGlucose uptakeArterial plasma glucose levelsHepatic sinusoidal insulinBasal plasma levelsNonhepatic glucose uptakeGlucose infusion rateHepatic glucose uptakeInhalation groupInsulin inhalationSubcutaneous insulinPeripheral veinPlasma levelsPortal veinPlasma insulin kineticsInsulin secretionInfusion rateInsulin actionGlucose utilizationInhalationThe 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-1
1997
Coadministration of glyburide and minoxidil, drugs with opposing effects on potassium channels
Stein C, Brown N, Carlson M, Campbell P, Wood A. Coadministration of glyburide and minoxidil, drugs with opposing effects on potassium channels. Clinical Pharmacology & Therapeutics 1997, 61: 662-668. PMID: 9209249, DOI: 10.1016/s0009-9236(97)90101-6.Peer-Reviewed Original ResearchConceptsBlood pressureHypotensive effectBlood pressure-lowering effectPotassium channelsIntravenous glucose tolerance testImportant pharmacodynamic interactionsSmall hypotensive responseDouble-blind fashionPressure-lowering effectCoadministration of drugsGlucose tolerance testSensitive potassium channelsSimilar significant decreaseBlood glucose concentrationHypotensive responsePharmacodynamic interactionsPharmacodynamic effectsSignificant hypoglycemiaHypoglycemic agentsTolerance testInsulin responseDrug interactionsHealthy subjectsHealthy volunteersHigh dose