Featured Publications
Stimulation of the hepatoportal nerve plexus with focused ultrasound restores glucose homoeostasis in diabetic mice, rats and swine
Cotero V, Graf J, Miwa H, Hirschstein Z, Qanud K, Huerta TS, Tai N, Ding Y, Jimenez-Cowell K, Tomaio JN, Song W, Devarajan A, Tsaava T, Madhavan R, Wallace K, Loghin E, Morton C, Fan Y, Kao TJ, Akhtar K, Damaraju M, Barenboim L, Maietta T, Ashe J, Tracey KJ, Coleman TR, Di Carlo D, Shin D, Zanos S, Chavan SS, Herzog RI, Puleo C. Stimulation of the hepatoportal nerve plexus with focused ultrasound restores glucose homoeostasis in diabetic mice, rats and swine. Nature Biomedical Engineering 2022, 6: 683-705. PMID: 35361935, PMCID: PMC10127248, DOI: 10.1038/s41551-022-00870-w.Peer-Reviewed Original ResearchConceptsGlucose homeostasisGlucose toleranceNerve plexusAfferent autonomic nervesHyperinsulinemic euglycaemic clampNon-pharmacologic therapiesType 2 diabetesInsulin-resistant diabetesHepatic portal systemAutonomic nervesNerve pathwaysDiabetic miceFocused ultrasound stimulationPeripheral neuronsSensory projectionsIntestinal tissueMetabolic diseasesMulti-omics profilingPortal systemMetabolic tissuesGlucose availabilityDiabetesSelective activationPlexusUltrasound stimulation
2017
β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares
Goldberg EL, Asher JL, Molony RD, Shaw AC, Zeiss CJ, Wang C, Morozova-Roche LA, Herzog RI, Iwasaki A, Dixit VD. β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares. Cell Reports 2017, 18: 2077-2087. PMID: 28249154, PMCID: PMC5527297, DOI: 10.1016/j.celrep.2017.02.004.Peer-Reviewed Original ResearchConceptsKetogenic dietGouty flaresΒ-hydroxybutyrateMajor risk factorAnti-inflammatory moleculesNLRP3-dependent mannerAlternate metabolic fuelsGout flaresJoint destructionIL-1βIntense painInterleukin-1βNLRP3 inflammasomeRisk factorsInflammatory neutrophilsBacterial infectionsNeutrophilsNLRP3Immune defenseGoutMetabolic fuelsBHBS100A9 fibrilsDietPain
2013
Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia
Herzog RI, Jiang L, Herman P, Zhao C, Sanganahalli BG, Mason GF, Hyder F, Rothman DL, Sherwin RS, Behar KL. Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia. Journal Of Clinical Investigation 2013, 123: 1988-1998. PMID: 23543056, PMCID: PMC3638906, DOI: 10.1172/jci65105.Peer-Reviewed Original ResearchConceptsAntecedent recurrent hypoglycemiaRecurrent hypoglycemiaHypoglycemic conditionsIntensive insulin therapyTight glycemic controlType 2 diabetesInsulin therapyGlycemic controlBrain metabolismElevated lactateNeuronal metabolismRodent modelsNeuronal activityGlucose metabolismHypoglycemiaLactate uptakeNeuronal functionType 1Metabolic regulatorOxidative capacityModest incrementLactateMetabolismUnexpected findingBrain
2009
Recurrent Antecedent Hypoglycemia Alters Neuronal Oxidative Metabolism In Vivo
Jiang L, Herzog RI, Mason GF, de Graaf RA, Rothman DL, Sherwin RS, Behar KL. Recurrent Antecedent Hypoglycemia Alters Neuronal Oxidative Metabolism In Vivo. Diabetes 2009, 58: 1266-1274. PMID: 19276443, PMCID: PMC2682668, DOI: 10.2337/db08-1664.Peer-Reviewed Original ResearchConceptsAntecedent recurrent hypoglycemiaAcute hypoglycemiaRecurrent hypoglycemiaEuglycemic conditionsGlucose utilizationRecurrent insulin-induced hypoglycemiaWhole-brain glucose metabolismNeuronal oxidative metabolismInsulin-induced hypoglycemiaHyperinsulinemic-hypoglycemic clampAntecedent hypoglycemiaPyruvate dehydrogenase fluxHigh glucose utilizationBrain metabolismRat modelHypoglycemiaGlucose metabolismHypoglycemic conditionsBrain metabolitesBrain functionTricarboxylic acid cycle activityOxidative metabolismEnergy substratesEuglycemiaInfusion
2008
Increased GABAergic Tone in the Ventromedial Hypothalamus Contributes to Suppression of Counterregulatory Reponses After Antecedent Hypoglycemia
Chan O, Cheng H, Herzog R, Czyzyk D, Zhu W, Wang A, McCrimmon RJ, Seashore MR, Sherwin RS. Increased GABAergic Tone in the Ventromedial Hypothalamus Contributes to Suppression of Counterregulatory Reponses After Antecedent Hypoglycemia. Diabetes 2008, 57: 1363-1370. PMID: 18375441, PMCID: PMC5518793, DOI: 10.2337/db07-1559.Peer-Reviewed Original ResearchConceptsVMH GABA levelsVentromedial hypothalamusGlutamic acid decarboxylaseHypoglycemic animalsHypoglycemic ratsSympathoadrenal responseRecurrent hypoglycemiaCounterregulatory responsesGABAergic toneInhibitory toneGABA levelsHypoglycemia-associated autonomic failureGABAergic inhibitory toneOnset of hypoglycemiaGABA synthetic enzymeQuantitative RT-PCRAntecedent hypoglycemiaAutonomic failureHypoglycemic stimulusReceptor blockadeEpinephrine releaseAcute hypoglycemiaReceptor antagonistInhibitory neurotransmitterSubsequent boutEffect of Acute and Recurrent Hypoglycemia on Changes in Brain Glycogen Concentration
Herzog RI, Chan O, Yu S, Dziura J, McNay EC, Sherwin RS. Effect of Acute and Recurrent Hypoglycemia on Changes in Brain Glycogen Concentration. Endocrinology 2008, 149: 1499-1504. PMID: 18187548, PMCID: PMC2276713, DOI: 10.1210/en.2007-1252.Peer-Reviewed Original ResearchConceptsHypoglycemia-associated autonomic failureRecurrent hypoglycemiaAcute hypoglycemiaAutonomic failureBrain glycogenGlycogen levelsBrain glucoseGlucose levelsRH groupInsulin-induced acute hypoglycemiaSimilar blood glucose levelsIntensive insulin treatmentHyperinsulinemic-hypoglycemic clamp studyBrain glycogen concentrationHypoglycemic clamp studiesBlood glucose levelsBrain glucose levelsCounterregulatory failureDiabetic patientsGlycogen supercompensationRecurrent episodesSingle boutInsulin treatmentClamp studiesAnimal models
2005
Pharmacological properties of neuronal TTX-resistant sodium channels and the role of a critical serine pore residue
Leffler A, Herzog RI, Dib-Hajj SD, Waxman SG, Cummins TR. Pharmacological properties of neuronal TTX-resistant sodium channels and the role of a critical serine pore residue. Pflügers Archiv - European Journal Of Physiology 2005, 451: 454-463. PMID: 15981012, DOI: 10.1007/s00424-005-1463-x.Peer-Reviewed Original Research
2003
Calmodulin Binds to the C Terminus of Sodium Channels Nav1.4 and Nav1.6 and Differentially Modulates Their Functional Properties
Herzog RI, Liu C, Waxman SG, Cummins TR. Calmodulin Binds to the C Terminus of Sodium Channels Nav1.4 and Nav1.6 and Differentially Modulates Their Functional Properties. Journal Of Neuroscience 2003, 23: 8261-8270. PMID: 12967988, PMCID: PMC6740705, DOI: 10.1523/jneurosci.23-23-08261.2003.Peer-Reviewed Original ResearchConceptsVoltage-gated sodium channelsSodium channelsNeuronal sodium channelsCalcium-independent mechanismVGSC isoformsNeuronal plasticityCell excitabilityNav1.6 channelsNav1.6Overexpression of CaMCalcium-dependent mannerCalcium-independent mannerNav1.4Sodium channel Nav1.4Channel Nav1.4Functional expressionCurrent amplitudeThe pentapeptide QYNAD does not block voltage-gated sodium channels
Cummins T, Renganathan M, Herzog R, Dib-Hajj S, Waxman S, Stys P, Horn R. The pentapeptide QYNAD does not block voltage-gated sodium channels. Neurology 2003, 60: 1871-1872. PMID: 12796562, DOI: 10.1212/wnl.60.11.1871-a.Peer-Reviewed Original ResearchThe pentapeptide QYNAD does not block voltage-gated sodium channels
Cummins TR, Renganathan M, Stys PK, Herzog RI, Scarfo K, Horn R, Dib-Hajj SD, Waxman SG. The pentapeptide QYNAD does not block voltage-gated sodium channels. Neurology 2003, 60: 224-229. PMID: 12552035, DOI: 10.1212/01.wnl.0000042423.36650.bd.Peer-Reviewed Original ResearchConceptsVoltage-gated sodium channelsSodium channelsDifferent sodium channel subtypesSodium currentDorsal root ganglion neuronsInflammatory neurologic disordersMajor sodium channelPatch-clamp recordingsSodium channel subtypesSodium channel functionNodes of RanvierPentapeptide QYNADOptic nerveGanglion neuronsIntact neuronsNeurologic disordersQYNADChannel subtypesHuman CSFAbnormal myelinFiber tractsElevated levelsEndogenous pentapeptideMicro MChannel function
2001
Nav1.3 Sodium Channels: Rapid Repriming and Slow Closed-State Inactivation Display Quantitative Differences after Expression in a Mammalian Cell Line and in Spinal Sensory Neurons
Cummins TR, Aglieco F, Renganathan M, Herzog RI, Dib-Hajj SD, Waxman SG. Nav1.3 Sodium Channels: Rapid Repriming and Slow Closed-State Inactivation Display Quantitative Differences after Expression in a Mammalian Cell Line and in Spinal Sensory Neurons. Journal Of Neuroscience 2001, 21: 5952-5961. PMID: 11487618, PMCID: PMC6763143, DOI: 10.1523/jneurosci.21-16-05952.2001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxotomyBiolisticsCells, CulturedGanglia, SpinalGene ExpressionGenes, ReporterHumansIon Channel GatingKidneyMaleMembrane PotentialsMutagenesis, Site-DirectedNeurons, AfferentPatch-Clamp TechniquesPolymerase Chain ReactionProtein SubunitsRatsReaction TimeSodiumSodium ChannelsSpinal CordTetrodotoxinConceptsNav1.3 channelsRapid reprimingHEK-293 cellsDRG neuronsTTX-sensitive sodium currentDorsal root ganglion neuronsNav1.3 sodium channelsSodium channelsSpinal sensory neuronsVoltage-gated sodium channelsSteady-state inactivationLarger ramp currentsHuman embryonic kidney 293 cellsPeripheral axotomyEmbryonic kidney 293 cellsGanglion neuronsSlow depolarizationSensory neuronsVoltage-dependent propertiesKidney 293 cellsSodium currentRamp currentsNav1.3NeuronsBeta2 subunit