2020
Non‐alcoholic Fatty Liver Disease and Insulin Resistance
Petersen M, Samuel V, Petersen K, Shulman G. Non‐alcoholic Fatty Liver Disease and Insulin Resistance. 2020, 455-471. DOI: 10.1002/9781119436812.ch37.Peer-Reviewed Original ResearchNon-alcoholic fatty liver diseaseHepatic insulin resistanceFatty liver diseaseInsulin resistanceLiver diseaseDevelopment of NAFLDLipid-induced muscle insulin resistanceRandle glucose-fatty acid cycleCommon chronic liver diseaseType 2 diabetes mellitusHyperinsulinemic-euglycemic clamp studiesGlucose-fatty acid cycleLiver-related deathSkeletal muscleChronic liver diseaseNon-alcoholic steatohepatitisMajor risk factorLipid-induced hepatic insulin resistanceMuscle insulin resistanceDiabetes mellitusRisk factorsClamp studiesLipoprotein lipaseDiseaseProtein kinase C
2018
GPR119 Agonism Increases Glucagon Secretion During Insulin-Induced Hypoglycemia
Li NX, Brown S, Kowalski T, Wu M, Yang L, Dai G, Petrov A, Ding Y, Dlugos T, Wood H, Wang L, Erion M, Sherwin R, Kelley DE. GPR119 Agonism Increases Glucagon Secretion During Insulin-Induced Hypoglycemia. Diabetes 2018, 67: db180031. PMID: 29669745, PMCID: PMC6014553, DOI: 10.2337/db18-0031.Peer-Reviewed Original ResearchConceptsSTZ-diabetic ratsGlucagon secretionGPR119 agonistsGlucagon counterregulatory responseGPR119 knockout miceIntensive insulin therapyInsulin-induced hypoglycemiaHypoglycemic clamp studiesG protein-coupled receptorsGPR119 agonismIncretin secretionInsulin therapyCounterregulatory responsesDiabetic rodentsHypoglycemic clampIatrogenic hypoglycemiaDiabetic ratsGlucagon releaseKO miceRecurrent boutsAgonist pretreatmentClamp studiesIsolated isletsStimulatory actionCultured islets
2013
CGI-58 knockdown sequesters diacylglycerols in lipid droplets/ER-preventing diacylglycerol-mediated hepatic insulin resistance
Cantley JL, Yoshimura T, Camporez JP, Zhang D, Jornayvaz FR, Kumashiro N, Guebre-Egziabher F, Jurczak MJ, Kahn M, Guigni BA, Serr J, Hankin J, Murphy RC, Cline GW, Bhanot S, Manchem VP, Brown JM, Samuel VT, Shulman GI. CGI-58 knockdown sequesters diacylglycerols in lipid droplets/ER-preventing diacylglycerol-mediated hepatic insulin resistance. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 1869-1874. PMID: 23302688, PMCID: PMC3562813, DOI: 10.1073/pnas.1219456110.Peer-Reviewed Original ResearchMeSH Keywords1-Acylglycerol-3-Phosphate O-AcyltransferaseAdipose Tissue, WhiteAnimalsCell MembraneDiet, High-FatDiglyceridesEndoplasmic ReticulumGene ExpressionGene Knockdown TechniquesHumansImmunoblottingInjections, IntraperitonealInsulin ResistanceLipidsLiverMaleMiceMice, Inbred C57BLOligonucleotides, AntisenseProtein Kinase C-epsilonProtein TransportReverse Transcriptase Polymerase Chain ReactionConceptsHepatic insulin resistanceInsulin resistanceHepatic steatosisCGI-58 knockdownHigh-fat fed miceHyperinsulinemic-euglycemic clamp studiesSevere hepatic steatosisCGI-58 expressionFat-fed miceLipid-induced hepatic insulin resistanceChanarin-Dorfman syndromeComparative gene identification-58Lipid droplet-associated proteinAdipose triglyceride lipaseDroplet-associated proteinAntisense oligonucleotide treatmentInsulin sensitivityASO treatmentClamp studiesLipotoxic conditionsKnockdown miceCGI-58PKCε activationMiceTriglyceride lipase
2011
Modulation of β-Adrenergic Receptors in the Ventromedial Hypothalamus Influences Counterregulatory Responses to Hypoglycemia
Szepietowska B, Zhu W, Chan O, Horblitt A, Dziura J, Sherwin RS. Modulation of β-Adrenergic Receptors in the Ventromedial Hypothalamus Influences Counterregulatory Responses to Hypoglycemia. Diabetes 2011, 60: 3154-3158. PMID: 22013013, PMCID: PMC3219955, DOI: 10.2337/db11-0432.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic beta-2 Receptor AgonistsAdrenergic beta-AntagonistsAnimalsBlood GlucoseEpinephrineEthanolaminesFormoterol FumarateGlucagonGlucose Clamp TechniqueHypoglycemiaImidazolesInsulinMaleNorepinephrinePropanolaminesRatsRats, Sprague-DawleyReceptors, Adrenergic, betaVentromedial Hypothalamic NucleusConceptsCounterregulatory responsesVentromedial hypothalamusGlucose counterregulationAwake male Sprague-Dawley ratsB2AR agonistMale Sprague-Dawley ratsCounterregulatory hormone releaseDefective glucose counterregulationExogenous glucose requirementsHyperinsulinemic-hypoglycemic clamp studySprague-Dawley ratsLocal catecholamine releaseArtificial extracellular fluidΒ-Adrenergic ReceptorsEpinephrine responseGlucagon responseDiabetic patientsEpinephrine releaseSimilar insulinCatecholamine releaseHormone releaseGuide cannulaeClamp studiesTherapeutic benefitHypoglycemia
2010
Early Pharmacokinetic and Pharmacodynamic Effects of Mixing Lispro With Glargine Insulin Results of glucose clamp studies in youth with type 1 diabetes
Cengiz E, Tamborlane WV, Martin-Fredericksen M, Dziura J, Weinzimer SA. Early Pharmacokinetic and Pharmacodynamic Effects of Mixing Lispro With Glargine Insulin Results of glucose clamp studies in youth with type 1 diabetes. Diabetes Care 2010, 33: 1009-1012. PMID: 20150302, PMCID: PMC2858163, DOI: 10.2337/dc09-2118.Peer-Reviewed Original ResearchConceptsType 1 diabetesGlucose clamp studiesGlucose excursionsClamp studiesMeal-related glucose excursionsRapid-acting insulin analoguesRapid-acting insulinEuglycemic glucose clampTime-action curvePharmacodynamic peakA1c levelsTreatment burdenPharmacodynamic effectsDaily injectionsUnits/Pharmacodynamic actionClinical studiesGlucose clampMixed injectionGlargineEarly pharmacokineticsInsulin analoguesObjective clinicianInsulin pharmacokineticsLispro
2009
Pancreatic perfusion of healthy individuals and type 1 diabetic patients as assessed by magnetic resonance perfusion imaging
Hirshberg B, Qiu M, Cali AM, Sherwin R, Constable T, Calle RA, Tal MG. Pancreatic perfusion of healthy individuals and type 1 diabetic patients as assessed by magnetic resonance perfusion imaging. Diabetologia 2009, 52: 1561. PMID: 19488737, DOI: 10.1007/s00125-009-1406-8.Peer-Reviewed Original ResearchConceptsType 1 diabetic patientsPancreatic blood flowDiabetic patientsBlood flowIslet massHealthy volunteersPancreatic perfusionArterial spin labeling magnetic resonanceTotal pancreatic blood flowPancreatic beta-cell massConclusions/interpretationOur dataAims/hypothesisLossBeta-cell massMagnetic resonance perfusionSignificant differencesHuman pancreatic isletsDiabetes mellitusVascularised organsIslet functionMurine modelClamp studiesNormal volunteersHealthy individualsPatientsControl tissuesMedium-Chain Fatty Acids Improve Cognitive Function in Intensively Treated Type 1 Diabetic Patients and Support In Vitro Synaptic Transmission During Acute Hypoglycemia
Page KA, Williamson A, Yu N, McNay EC, Dzuira J, McCrimmon RJ, Sherwin RS. Medium-Chain Fatty Acids Improve Cognitive Function in Intensively Treated Type 1 Diabetic Patients and Support In Vitro Synaptic Transmission During Acute Hypoglycemia. Diabetes 2009, 58: 1237-1244. PMID: 19223595, PMCID: PMC2671041, DOI: 10.2337/db08-1557.Peer-Reviewed Original ResearchConceptsType 1 diabetic subjectsMedium-chain triglyceridesSynaptic transmissionDiabetic subjectsMedium-chain triglyceride ingestionType 1 diabetic patientsRat hippocampal slice preparationHippocampal synaptic transmissionBeta-hydroxybutyrate levelsType 1 diabetesHypoglycemic clamp studiesHippocampal slice preparationControl glucose concentrationsTriglyceride ingestionDiabetic patientsFatty acidsAcute hypoglycemiaSymptomatic responseHippocampal slicesSlice preparationFree fatty acidsGlucose levelsClamp studiesTherapeutic advantageNeuronal activity
2008
Effect 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
2006
Effects of hypoglycemia on human brain activation measured with fMRI
Anderson AW, Heptulla RA, Driesen N, Flanagan D, Goldberg PA, Jones TW, Rife F, Sarofin H, Tamborlane W, Sherwin R, Gore JC. Effects of hypoglycemia on human brain activation measured with fMRI. Magnetic Resonance Imaging 2006, 24: 693-697. PMID: 16824963, DOI: 10.1016/j.mri.2006.03.013.Peer-Reviewed Original ResearchConceptsFunctional magnetic resonance imagingBrain activationHuman brain activationPassive sensory stimulationCognitive tasksFMRI activityVisual stimuliEuglycemic clamp studiesBlood glucose levelsLevel-dependent contrastEffects of hypoglycemiaBOLD signalSensory stimulationHealthy human subjectsVisual stimulationMagnetic resonance imagingHyperinsulinemic hypoglycemicHealthy brainAcute hypoglycemiaGlucose levelsClamp studiesResonance imagingFractional signal changeHypoglycemiaEuglycemia
2004
Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes
Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes. New England Journal Of Medicine 2004, 350: 664-671. PMID: 14960743, PMCID: PMC2995502, DOI: 10.1056/nejmoa031314.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAdipose TissueBlood GlucoseDiabetes Mellitus, Type 2Fatty AcidsFemaleGlucoseGlucose Clamp TechniqueGlucose Tolerance TestGlycerolHumansInsulinInsulin ResistanceLipolysisMagnetic Resonance SpectroscopyMaleMitochondriaMuscle, SkeletalOxidative PhosphorylationTriglyceridesConceptsInsulin-resistant offspringType 2 diabetesIntramyocellular lipid contentInsulin-sensitive control subjectsMagnetic resonance spectroscopy studyInsulin resistanceControl subjectsProton magnetic resonance spectroscopy studyHyperinsulinemic-euglycemic clamp studiesTumor necrosis factor alphaImpaired mitochondrial activityIntrahepatic triglyceride contentDevelopment of diabetesChildren of patientsInsulin-resistant subjectsNecrosis factor alphaSensitivity of liverInsulin-stimulated ratesFatty acid metabolismMitochondrial oxidative phosphorylation activityInterleukin-6Intramyocellular lipidsPlasma concentrationsFactor alphaClamp studiesLocal anesthetic effects of cocaethylene and isopropylcocaine on rat peripheral nerves
Tokuno HA, Bradberry CW, Everill B, Agulian SK, Wilkes S, Baldwin RM, Tamagnan GD, Kocsis JD. Local anesthetic effects of cocaethylene and isopropylcocaine on rat peripheral nerves. Brain Research 2004, 996: 159-167. PMID: 14697493, DOI: 10.1016/j.brainres.2003.10.024.Peer-Reviewed Original ResearchConceptsAgonist substitution therapyLocal anesthetic propertiesCompound action potentialSubstitution therapyDorsal rootsAnesthetic propertiesCocaine rewardDorsal root ganglion neuronsSucrose gap chamberUse-dependent blockadeRat peripheral nerveLocal anesthetic effectRat sciatic nerveDopamine uptake inhibitorPotential pharmacological toolsPatch-clamp studiesCAP amplitudeGanglion neuronsSciatic nervePeripheral nervesClinical studiesTreatment candidatesClamp studiesStimulus trainsImpulse blockade
2002
Striking Differences in Glucose and Lactate Levels between Brain Extracellular Fluid and Plasma in Conscious Human Subjects: Effects of Hyperglycemia and Hypoglycemia
Abi-Saab WM, Maggs DG, Jones T, Jacob R, Srihari V, Thompson J, Kerr D, Leone P, Krystal JH, Spencer DD, During MJ, Sherwin RS. Striking Differences in Glucose and Lactate Levels between Brain Extracellular Fluid and Plasma in Conscious Human Subjects: Effects of Hyperglycemia and Hypoglycemia. Cerebrovascular And Brain Metabolism Reviews 2002, 22: 271-279. PMID: 11891432, DOI: 10.1097/00004647-200203000-00004.Peer-Reviewed Original ResearchConceptsConscious human subjectsBrain extracellular fluidLactate levelsECF levelsExtracellular fluidBasal conditionsGlucose-derived lactateEffects of hyperglycemiaHuman subjectsECF glucoseElectrophysiologic evaluationIntracerebral microdialysisIntractable epilepsyBrain levelsMetabolic milieuClamp studiesBrainAnaerobic glycolysisHuman dataLactateGlucoseLow levelsSubjectsHigh levelsLevels
1999
Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats
Jiang Z, Lin Y, Clemont A, Feener E, Hein K, Igarashi M, Yamauchi T, White M, King G. Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats. Journal Of Clinical Investigation 1999, 104: 447-457. PMID: 10449437, PMCID: PMC408521, DOI: 10.1172/jci5971.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaCalcium-Calmodulin-Dependent Protein KinasesIn Vitro TechniquesInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsLiverMaleMicrocirculationObesityPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationRatsRats, ZuckerReceptor, InsulinRecombinant ProteinsSignal TransductionTyrosineConceptsObese ratsLean ratsObese ZuckerIRS-2-associated PIIndependent risk factorProtein levelsEuglycemic clamp studiesInsulin-resistant statesObese Zucker ratsSelective resistanceTyrosine phosphorylationVascular tissueInsulin resistanceInsulin infusionRisk factorsCardiovascular diseaseClamp studiesZucker ratsReceptor beta subunitAortaRatsInsulinInsulin receptor beta subunitERK 1/2Vivo studies
1998
Properties of human glial cells associated with epileptic seizure foci
Bordey A, Sontheimer H. Properties of human glial cells associated with epileptic seizure foci. Epilepsy Research 1998, 32: 286-303. PMID: 9761328, DOI: 10.1016/s0920-1211(98)00059-x.Peer-Reviewed Original ResearchConceptsSeizure focusGlial cellsMesio-temporal lobe epilepsyWhole-cell patch-clamp recordingsLucifer YellowControl rat hippocampusPathophysiology of seizuresSlow action potentialsCurrent-clamp studiesGFAP-positive astrocytesEpileptic seizure fociPatch-clamp recordingsHuman glial cellsLobe epilepsyAcute slicesRat hippocampusEpilepsy patientsClamp studiesRat astrocytesAstrocytesIntermediate filaments GFAPNormal astrocytesAction potentialsPhysiological propertiesBranched processes
1994
Progesterone administration induced impairment of insulin suppression of hepatic glucose production
Nelson T, Shulman G, Grainger D, Diamond M. Progesterone administration induced impairment of insulin suppression of hepatic glucose production. Fertility And Sterility 1994, 62: 491-496. PMID: 8062943, DOI: 10.1016/s0015-0282(16)56936-2.Peer-Reviewed Original ResearchComparison of the metabolic effects of recombinant human insulin-like growth factor-I and insulin. Dose-response relationships in healthy young and middle-aged adults.
Boulware SD, Tamborlane WV, Rennert NJ, Gesundheit N, Sherwin RS. Comparison of the metabolic effects of recombinant human insulin-like growth factor-I and insulin. Dose-response relationships in healthy young and middle-aged adults. Journal Of Clinical Investigation 1994, 93: 1131-1139. PMID: 8132753, PMCID: PMC294058, DOI: 10.1172/jci117065.Peer-Reviewed Original ResearchConceptsRecombinant human insulin-like growth factorInsulin-like growth factorHuman insulin-like growth factorMiddle-aged subjectsC-peptideYoung subjectsBasal IGF-I levelsHealthy middle-aged subjectsGlucose uptakeGrowth factorAdverse metabolic changesFree fatty acid levelsIGF-I levelsRelative insulin deficiencyEuglycemic clamp studiesFat oxidation rateDose-response relationshipFatty acid levelsInsulin-induced stimulationMiddle-aged adultsBasal insulinInsulin deficiencyMetabolic effectsClamp studiesRhIGF
1993
Inhibitory Effect of Pregnancy on Counterregulatory Hormone Responses to Hypoglycemia in Awake Rat
Rossi G, Lapaczewski P, Diamond M, Jacob R, Shulman G, Sherwin R. Inhibitory Effect of Pregnancy on Counterregulatory Hormone Responses to Hypoglycemia in Awake Rat. Diabetes 1993, 42: 1440-1445. PMID: 8375583, DOI: 10.2337/diab.42.10.1440.Peer-Reviewed Original ResearchConceptsPregnant ratsGlucagon responseNonpregnant controlsAwake pregnant ratsCounterregulatory hormone responsesIntensive insulin treatmentRelease of epinephrineHypoglycemia risk factorsHypoglycemic clamp studiesDiabetic pregnanciesGlucose counterregulationMaternal hypoglycemiaHypoglycemic stimulusEpinephrine releaseEpinephrine levelsMild hypoglycemiaBrisk responseNonfasting stateRisk factorsAwake ratsInsulin treatmentKetone levelsClamp studiesGlucose levelsNonfasted state
1991
SUPPRESSION OF COUNTERREGULATORY HORMONE RESPONSE TO HYPOGLYCEMIA BY INSULIN PER SE
DIAMOND M, HALLARMAN L, STARICK-ZYCH K, JONES T, CONNOLLY-HOWARD M, TAMBORLANE W, SHERWIN R. SUPPRESSION OF COUNTERREGULATORY HORMONE RESPONSE TO HYPOGLYCEMIA BY INSULIN PER SE. The Journal Of Clinical Endocrinology & Metabolism 1991, 72: 1388-1390. PMID: 2026760, DOI: 10.1210/jcem-72-6-1388.Peer-Reviewed Original ResearchConceptsCounterregulatory hormone responsesHormone responseGlucose levelsNormal subjectsCounterregulatory hormone levelsResponses of epinephrineVariable glucose infusionDegree of hyperinsulinemiaHigh-dose studiesHypoglycemic clamp studiesHypoglycemic counterregulationHypoglycemic stimulusInsulin doseExogenous insulinDose studyHormone levelsGlucose infusionClamp studiesHypoglycemiaGrowth hormoneHypoglycemic plateauInsulinModulating effectOnly variableHyperinsulinemiaIsolated supporting cells from the organ of Corti: Some whole cell electrical characteristics and estimates of gap junctional conductance
Santos-Sacchi J. Isolated supporting cells from the organ of Corti: Some whole cell electrical characteristics and estimates of gap junctional conductance. Hearing Research 1991, 52: 89-98. PMID: 2061216, DOI: 10.1016/0378-5955(91)90190-k.Peer-Reviewed Original ResearchConceptsInput resistanceWhole-cell voltage clamp studiesAverage input resistanceHensen's cellsOrgan of CortiVoltage-clamp studiesGuinea pig organJunctional resistanceClamp studiesCell levelPig organsSingle-cell levelGap junctional conductanceG omegaElectrical activityExternal TEACell couplingCortiJunctional conductanceCellsOrgansSensitive indicatorSmall groupCell valuesInsulin Resistance of Puberty: a Defect Restricted to Peripheral Glucose Metabolism*
AMIEL S, CAPRIO S, SHERWIN R, PLEWE G, HAYMOND M, TAMBORLANE W. Insulin Resistance of Puberty: a Defect Restricted to Peripheral Glucose Metabolism*. The Journal Of Clinical Endocrinology & Metabolism 1991, 72: 277-282. PMID: 1991798, DOI: 10.1210/jcem-72-2-277.Peer-Reviewed Original ResearchConceptsPeripheral glucose metabolismInsulin resistancePubertal childrenGlucose metabolismHigher insulin doseMU/m2Hyperglycemic clamp studiesEuglycemic insulin clampEnhanced insulin responseHepatic glucose productionSelective insulin resistanceChain amino acidsHealthy prepubertalCompensatory hyperinsulinemiaInsulin doseInsulin clampPeripheral glucoseInsulin responsePlasma levelsPrepubertal childrenClamp studiesProtein anabolismNormal pubertyGlucose productionAmino acid metabolism
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply