2025
1727-P: Reduced Aromatic Amino Acid Suppression during Acute Hyperglycemia in Young Adults with Obesity
MATSON B, GUNAWAN F, ROTHMAN D, MASON G, NEWGARD C, HWANG J. 1727-P: Reduced Aromatic Amino Acid Suppression during Acute Hyperglycemia in Young Adults with Obesity. Diabetes 2025, 74 DOI: 10.2337/db25-1727-p.Peer-Reviewed Original ResearchCentral nervous systemAcute hyperglycemiaLean controlsBrain glucose levelsMass spectrometry-based metabolomic profilingMeasured plasma amino acidsInsulin resistanceGlucose levelsBranched chain amino acidsPlasma amino acidsDevelopment of insulin resistanceAromatic amino acid levelsChain amino acidsAcid suppressionResponse to hyperglycemiaMetabolomic profilesImpaired suppressionHyperglycemic clampObesityInsulin sensitivityHyperglycemiaNervous systemAmino acid changesBrain glucoseHealthy adults358-OR: Acute Fatty Acid Elevation Does Not Alter Brain Glucose Uptake in Humans
MATSON B, CHANG W, PALMIOTTO J, ROTHMAN D, BELFORT DE AGUIAR R, MASON G, HWANG J. 358-OR: Acute Fatty Acid Elevation Does Not Alter Brain Glucose Uptake in Humans. Diabetes 2025, 74 DOI: 10.2337/db25-358-or.Peer-Reviewed Original ResearchElevation of non-esterified fatty acidsNon-esterified fatty acid levelsHyperglycemic clampBrain glucose uptakeCirculating non-esterified fatty acidsBrain glucoseAcute elevationIntralipid infusionInsulin resistanceIntravenous infusion of salineAbsence of insulin resistanceNon-esterified fatty acidsInduce peripheral insulin resistanceHealthy adultsInfusion of salinePresence of hyperglycemiaGlucose uptakeMeasures of insulin sensitivityPeripheral insulin resistanceHigh-fat dietGlucose infusion rateIntravenous infusionPlasma glucoseLean individualsMRS scans
2024
12241 Association Between Brain Glucose And Circulating Glucagon Levels In Response To Acute Hyperglycemia
Matson B, Gunawan F, Coppoli A, Jiang L, Rangel E, De Aguiar R, Rothman D, Mason G, Hwang J. 12241 Association Between Brain Glucose And Circulating Glucagon Levels In Response To Acute Hyperglycemia. Journal Of The Endocrine Society 2024, 8: bvae163.674. PMCID: PMC11454728, DOI: 10.1210/jendso/bvae163.674.Peer-Reviewed Original ResearchCentral nervous systemBrain glucose levelsPlasma glucagon levelsHyperglycemic clampType 2 diabetesGlucagon levelsGlucagon secretionGlucose levelsResponse to hyperglycemiaAcute hyperglycemiaOral glucose tolerance testBrain glucose metabolismResponse to central nervous systemPathophysiology of type 2 diabetesResponse to hypoglycemiaBrain glucoseIndices of insulin sensitivityEffect of obesityRegulation of glucagon secretionGlucose tolerance testConsequences of obesityModulating glucagon secretionOvert metabolic abnormalitiesBrain glucose uptakeCirculating glucagon levelsDeficits in brain glucose transport among younger adults with obesity
Gunawan F, Matson B, Coppoli A, Jiang L, Ding Y, Perry R, Sanchez‐Rangel E, DeAguiar R, Behar K, Rothman D, Mason G, Hwang J. Deficits in brain glucose transport among younger adults with obesity. Obesity 2024, 32: 1329-1338. PMID: 38764181, PMCID: PMC11966602, DOI: 10.1002/oby.24034.Peer-Reviewed Original ResearchBrain glucose transportLean participantsMarkers of insulin resistanceMagnetic resonance spectroscopy scansEffect of obesityAssociated with alterationsLong-term brain functionCerebral glucose metabolic rateGlucose transportGlucose metabolic rateCardiometabolic comorbiditiesBrain energy utilizationPeripheral markersHyperglycemic clampInsulin resistanceObesityBrain glucose uptakeHuman findingsEating behaviorsYounger ageYoung healthy participantsNeurocognitive functionGlucose transport capacityBrain functionNonesterified fatty acids
2020
A Reduced Incretin Effect Mediated by the rs7903146 Variant in the TCF7L2 Gene Is an Early Marker of β-Cell Dysfunction in Obese Youth
Galderisi A, Tricò D, Pierpont B, Shabanova V, Samuels S, Man C, Galuppo B, Santoro N, Caprio S. A Reduced Incretin Effect Mediated by the rs7903146 Variant in the TCF7L2 Gene Is an Early Marker of β-Cell Dysfunction in Obese Youth. Diabetes Care 2020, 43: 2553-2563. PMID: 32788279, PMCID: PMC7510033, DOI: 10.2337/dc20-0445.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAllelesBiomarkersEarly DiagnosisFemaleGenotypeGlucose IntoleranceGlucose Tolerance TestHumansIncretinsInsulinInsulin ResistanceInsulin SecretionInsulin-Secreting CellsMalePancreatic DiseasesPediatric ObesityPolymorphism, Single NucleotideTranscription Factor 7-Like 2 ProteinYoung AdultConceptsOral glucose tolerance testIncretin effectRs7903146 variantObese youthVariant rs7903146Obese adolescentsHyperglycemic clampInsulin sensitivityInsulin secretionC-peptide secretion rateIsoglycemic intravenous glucose infusionGlucose-induced insulin secretionImpaired glucose toleranceMetabolic phenotypeGlucose tolerance testLower insulin secretionPlasma glucose peakIntravenous glucose infusionΒ-cell functionPlasma glucose concentrationΒ-cell dysfunctionT risk alleleTranscription factor 7Wild-type genotypeIncretin response1772-P: Reversibility of Altered Brain Glucose Kinetics in T2DM
RANGEL E, GUNAWAN F, JIANG L, SAVOYE M, DAI F, ROTHMAN D, MASON G, HWANG J. 1772-P: Reversibility of Altered Brain Glucose Kinetics in T2DM. Diabetes 2020, 69 DOI: 10.2337/db20-1772-p.Peer-Reviewed Original ResearchBrain glucose levelsPoor glycemic controlGlycemic controlGlucose levelsCentral nervous system complicationsNervous system complicationsBrain glucose transportPlasma glucose levelsContinuous glucose monitoringUncontrolled T2DMT2DM subjectsSystem complicationsBMI changeHyperglycemic clampHealthy controlsDiabetes regimenPost interventionHierarchical linear regression modelsGlucose time coursesMagnetic resonance spectroscopyHbA1cGlucose kineticsGlucose monitoringNational InstituteT2DM
2019
1835-P: Deletion of Insulin Receptor Substrate 2 in AGRP Neurons Causes Beta-Cell Dysfunction
TAO R, COPPS K, WHITE M, STOEHR O. 1835-P: Deletion of Insulin Receptor Substrate 2 in AGRP Neurons Causes Beta-Cell Dysfunction. Diabetes 2019, 68 DOI: 10.2337/db19-1835-p.Peer-Reviewed Original ResearchAgRP neuronsArcuate nucleusInsulin resistanceInsulin secretionInsulin receptor substrateType 2 diabetes progressesCompensatory insulin secretionL-arginine treatmentBeta-cell compensationBeta-cell dysfunctionPeripheral insulin resistanceBeta-cell failureBeta-cell functionHigh-fat dietInsulin secretory functionType 2 diabetesSteady-state hyperglycemiaGlucose infusion rateΒ-cell dysfunctionInsulin receptor substrate 2Pancreatic β-cellsGrowth-promoting actionDiabetes progressesFat dietHyperglycemic clamp
2018
PEPCK1 Antisense Oligonucleotide Prevents Adiposity and Impairs Hepatic Glycogen Synthesis in High-Fat Male Fed Rats
Beddow SA, Gattu AK, Vatner DF, Paolella L, Alqarzaee A, Tashkandi N, Popov V, Church C, Rodeheffer M, Cline G, Geisler J, Bhanot S, Samuel VT. PEPCK1 Antisense Oligonucleotide Prevents Adiposity and Impairs Hepatic Glycogen Synthesis in High-Fat Male Fed Rats. Endocrinology 2018, 160: 205-219. PMID: 30445425, PMCID: PMC6307100, DOI: 10.1210/en.2018-00630.Peer-Reviewed Original ResearchMeSH KeywordsAdipose Tissue, WhiteAdiposityAnimalsDiabetes Mellitus, Type 2Diet, High-FatGlucokinaseHumansInsulinIntracellular Signaling Peptides and ProteinsLipogenesisLiverLiver GlycogenMaleMiceMice, Inbred C57BLOligonucleotides, AntisensePhosphoenolpyruvate Carboxykinase (GTP)RatsRats, Sprague-DawleyConceptsHepatic glycogen synthesisAdipose tissueAntisense oligonucleotideType 2 diabetes mellitusWhite adipose tissue massIncreased hepatic gluconeogenesisChow fed ratsHepatic insulin sensitivityMale Sprague-DawleyAdipose tissue massHepatic insulin resistanceWhite adipose tissueHepatic glucose productionDe novo lipogenesisHepatic glucokinase expressionControl antisense oligonucleotideGlycogen synthesisTranscription factor 3HFF ratsDiabetes mellitusHepatic steatosisInsulin resistanceHyperglycemic clampPlasma glucoseInsulin sensitivityGlycemic Variability and Brain Glucose Levels in T1DM
Hwang JJ, Jiang L, Sanchez Rangel E, Fan X, Ding Y, Lam W, Leventhal J, Dai F, Rothman DL, Mason GF, Sherwin RS. Glycemic Variability and Brain Glucose Levels in T1DM. Diabetes 2018, 68: db180722. PMID: 30327383, PMCID: PMC6302539, DOI: 10.2337/db18-0722.Peer-Reviewed Original ResearchConceptsBrain glucose levelsGlycemic variabilityGlucose levelsHyperglycemic clampType 1 diabetes mellitusPlasma glucose levelsBrain glucose transportHealthy control participantsDiabetes mellitusBrain glucoseControl ratsContinuous glucose monitorGlucose clampRat modelOccipital lobeMRS scanningT1DMGlucose kineticsControl participantsGlucose transport kineticsGlucose monitorSimilar changesRatsClampGlucose transportShort-Term Weight Loss Undermines Brain Regulation of Food Consumption
LAM W, SEO D, LACADIE C, SCHMIDT C, ROSENBERG S, HOANG H, HWANG J, CONSTABLE T, SAVOYE M, SINHA R, SHERWIN R, BELFORT-DEAGUIAR R. Short-Term Weight Loss Undermines Brain Regulation of Food Consumption. Diabetes 2018, 67 DOI: 10.2337/db18-1802-p.Peer-Reviewed Original ResearchWeight lossTest mealBrain regulationAd libitum test mealShort-term weight lossFunctional MRIBrain activityWeight loss maintenanceTotal calorie intakePost-prandial hyperglycemiaFood consumptionHigh-calorie food picturesMannKind CorporationSuppress appetiteCalorie dietOB subjectsLoss maintenanceObese individualsHyperglycemic clampRegeneron PharmaceuticalsAppetite controlFood intakeCalorie intakeGlaxoSmithKline plcHyperglycemia
2017
Blunted rise in brain glucose levels during hyperglycemia in adults with obesity and T2DM
Hwang JJ, Jiang L, Hamza M, Rangel E, Dai F, Belfort-DeAguiar R, Parikh L, Koo BB, Rothman DL, Mason G, Sherwin RS. Blunted rise in brain glucose levels during hyperglycemia in adults with obesity and T2DM. JCI Insight 2017, 2: e95913. PMID: 29046482, PMCID: PMC5846903, DOI: 10.1172/jci.insight.95913.Peer-Reviewed Original ResearchConceptsGlucose levelsPlasma free fatty acid levelsSimilar plasma glucose levelsFree fatty acid levelsCerebral glucose metabolismPlasma glucose levelsBrain glucose levelsFatty acid levelsAltered feeding behaviorGlucose incrementHyperglycemic clampBrain glucoseCerebral functionLean participantsOccipital lobeRodent modelsGlucose metabolismObesityT2DMGlucose responseHyperglycemiaNeurocognitive consequencesSimilar findingsAcid levelsIntracerebral glucoseThe human brain produces fructose from glucose
Hwang JJ, Jiang L, Hamza M, Dai F, Belfort-DeAguiar R, Cline G, Rothman DL, Mason G, Sherwin RS. The human brain produces fructose from glucose. JCI Insight 2017, 2: e90508. PMID: 28239653, PMCID: PMC5313070, DOI: 10.1172/jci.insight.90508.Peer-Reviewed Original ResearchConceptsPolyol pathwayFructose levelsIntracerebral glucoseBlood-brain barrierPathogenesis of obesityType 2 diabetesEffects of fructoseHuman brainRegression model analysisCNS deliveryCNS effectsHyperglycemic clampHealthy subjectsDietary consumptionGlucoseBaselineBrainMixed-effects regression model analysisFeeding behaviorMinutesCN productionObesityDiabetesLevelsPathogenesis
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 variantsCo-occurrence of Risk Alleles in or Near Genes Modulating Insulin Secretion Predisposes Obese Youth to Prediabetes
Giannini C, Man C, Groop L, Cobelli C, Zhao H, Shaw MM, Duran E, Pierpont B, Bale AE, Caprio S, Santoro N. Co-occurrence of Risk Alleles in or Near Genes Modulating Insulin Secretion Predisposes Obese Youth to Prediabetes. Diabetes Care 2014, 37: 475-482. PMID: 24062323, PMCID: PMC3898754, DOI: 10.2337/dc13-1458.Peer-Reviewed Original ResearchConceptsIGT/T2DImpaired glucose toleranceNormal glucose toleranceInsulin secretionRisk allelesGlucose toleranceObese childrenChance of progressionType 2 diabetesHigh genetic predispositionHigh-risk scoreOral minimal modelObese subjectsPediatric obesityProgressive worseningHyperglycemic clampObese youthHigh riskLower oddsRisk scoreGenetic predispositionT2DSecretionGene variantsEarly phase
2011
Regulation of hepatic fat and glucose oxidation in rats with lipid‐induced hepatic insulin resistance
Alves TC, Befroy DE, Kibbey RG, Kahn M, Codella R, Carvalho RA, Petersen K, Shulman GI. Regulation of hepatic fat and glucose oxidation in rats with lipid‐induced hepatic insulin resistance. Hepatology 2011, 53: 1175-1181. PMID: 21400553, PMCID: PMC3077048, DOI: 10.1002/hep.24170.Peer-Reviewed Original ResearchConceptsLipid-induced hepatic insulin resistanceHepatic insulin resistanceInsulin resistanceTricarboxylic acid fluxFatty acid oxidationPyruvate dehydrogenaseHyperinsulinemic-euglycemic clampHyperinsulinemic-hyperglycemic clampInfusion of somatostatinSubstrate availabilityHigh-fat dietPlasma glucose concentrationRegulationCritical rolePyruvate dehydrogenase fluxHepatic fatHyperglycemic clampAcid oxidationAwake ratsBasal concentrations
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