2025
358-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 scansReduced Notch signaling in hypothalamic endothelial cells mediates obesity-induced alterations in glucose uptake and insulin signaling
Zhu Y, Mehlkop O, Backes H, Cremer A, Porniece M, Klemm P, Steuernagel L, Chen W, Johnen R, Wunderlich F, Jais A, Brüning J. Reduced Notch signaling in hypothalamic endothelial cells mediates obesity-induced alterations in glucose uptake and insulin signaling. Cell Reports 2025, 44: 115522. PMID: 40186867, DOI: 10.1016/j.celrep.2025.115522.Peer-Reviewed Original ResearchConceptsShort-term HFD feedingNotch signalingIntracellular domainGlucose uptakeBrain microvascular endothelial cellsNotch intracellular domainHFD feedingDownregulation of Notch signalingHigh-fat dietBlood-brain barrierReduced Notch signalingGLUT1 expressionInsulin signalingSystemic insulin sensitivityBlood-brain barrier permeabilityNotch activationInduced expressionObesity-induced alterationsCaveolae formationPleiotropic effectsEndothelial cellsMicrovascular endothelial cellsExpressionBlood-brain barrier functionCultured brain microvascular endothelial cellsImpacts of Obesity-Induced Insulin and Leptin Dysregulation on Ovarian Function and Fertility
Rodriguez Y, Yang-Hartwich Y, Perry R. Impacts of Obesity-Induced Insulin and Leptin Dysregulation on Ovarian Function and Fertility. Physiology 2025, 40: 1996. DOI: 10.1152/physiol.2025.40.s1.1996.Peer-Reviewed Original ResearchOvarian functionOvarian tissueObesogenic contextRestore ovarian functionOvarian cell functionsResponse to hormonal changesCell viabilityImpact reproductive healthChow-fed controlsHuman granulosa-like tumorGlucose uptakeImproving fertility outcomesPotential therapeutic interventionsLeptin dysregulationCell proliferation assayHFD-fed miceLeptin treatmentGranulosa cellsLeptin resistanceOvarian environmentOvarian cellsReduced cell viabilityHormonal dysregulationLeptin signalingInsulin treatmentOlanzapine Induces Adipogenesis and Glucose Uptake by Activating Glycolysis and Synergizing with the PI3K-AKT Pathway
Li S, Fu Y, Wang W, Qiu J, Huang Y, Li X, Yang K, Yu X, Ma Y, Zhang Y, Zhang M, Li J, Li W. Olanzapine Induces Adipogenesis and Glucose Uptake by Activating Glycolysis and Synergizing with the PI3K-AKT Pathway. Current Neuropharmacology 2025, 23: 412-425. PMID: 39150031, PMCID: PMC12105311, DOI: 10.2174/1570159x22666240815120547.Peer-Reviewed Original ResearchAdministration of olanzapineTreated with olanzapineReactive oxygen speciesDownstream PI3K-Akt signal pathwayAssociated with obesityActive glycolysisAssessed body weightWeight gainDifferentiated 3T3-L1 preadipocytesLiver fat levelsPI3K-Akt pathwayOlanzapineDrug doseFemale miceDietary patternsMetabolic markersPI3K-AktFood intakeGlucose uptakeMouse modelGlycolipid abnormalitiesRodent modelsBody weightGAPDH expressionSignaling pathway
2024
UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling
Harrison A, Yang D, Cahoon J, Geng T, Cao Z, Karginov T, Hu Y, Li X, Chiari C, Qyang Y, Vella A, Fan Z, Vanaja S, Rathinam V, Witczak C, Bogan J, Wang P. UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling. Nature Immunology 2024, 25: 2234-2246. PMID: 39567760, PMCID: PMC12067455, DOI: 10.1038/s41590-024-02004-7.Peer-Reviewed Original ResearchConceptsRIG-I-like receptorsRIG-I-like receptor signalingCytosolic RIG-I-like receptorsAntiviral immunityPlasma membrane tetheringRNA virus infectionGlucose transportInnate antiviral immunityCytoplasmic RIG-I-like receptorsGolgi matrixGLUT4 translocationRLR signalingViral RNACell surfaceGLUT4GLUT4 expressionGlucose uptakeInterferon responseRNAGlycolytic reprogrammingVirus infectionHuman inflammatory myopathiesGolgiSignalUbiquitinSustained caloric restriction potentiates insulin action by activating prostacyclin synthase
Merali C, Quinn C, Huffman K, Pieper C, Bogan J, Barrero C, Merali S. Sustained caloric restriction potentiates insulin action by activating prostacyclin synthase. Obesity 2024, 32: 2286-2298. PMID: 39420421, PMCID: PMC12034231, DOI: 10.1002/oby.24150.Peer-Reviewed Original ResearchMolecular mechanismsIncreased GLUT4 translocationComplex molecular mechanismsGlucose uptake regulationUBX domainIncreased glucose uptakeGLUT4 translocationGLUT4 functionCaloric restrictionPTGIS expressionProteomic profilingCell surfaceCleavage pathwayInsulin sensitivityHuman adipocytesAdipose tissueGlucose uptakeGLUT4Enhanced insulin sensitivityInsulin receptor densityInsulin actionRisk of metabolic disordersCell membraneProstacyclin synthaseMonths of CRDepletion of TBC1D4 Improves the Metabolic Exercise Response by Overcoming Genetically Induced Peripheral Insulin Resistance.
Springer C, Binsch C, Weide D, Toska L, Cremer A, Backes H, Scheel A, Espelage L, Kotzka J, Sill S, Kurowski A, Kim D, Karpinski S, Schnurr T, Hansen T, Hartwig S, Lehr S, Cames S, Brüning J, Lienhard M, Herwig R, Börno S, Timmermann B, Al-Hasani H, Chadt A. Depletion of TBC1D4 Improves the Metabolic Exercise Response by Overcoming Genetically Induced Peripheral Insulin Resistance. Diabetes 2024, 73: 1058-1071. PMID: 38608276, DOI: 10.2337/db23-0463.Peer-Reviewed Original ResearchWhite adipose tissueLoss-of-function variantsAnalysis of glucose uptakeRegulation of glucose transportInterscapular brown adipose tissueHigh-fat dietEnhanced expression levelsDevelopment of insulin resistanceBrown adipose tissueMitochondrial activityTBC1D4Gene variantsInsulin resistanceAdipose tissueGlucose uptakePeripheral insulin resistanceGlucose transportExpression levelsGenesPrecision medicineInsulin toleranceGeneticsIncreased glucose clearanceExercise responseIn vivoActivation of GFRAL+ neurons induces hypothermia and glucoregulatory responses associated with nausea and torpor
Engström Ruud L, Font-Gironès F, Zajdel J, Kern L, Teixidor-Deulofeu J, Mannerås-Holm L, Carreras A, Becattini B, Björefeldt A, Hanse E, Fenselau H, Solinas G, Brüning J, Wunderlich T, Bäckhed F, Ruud J. Activation of GFRAL+ neurons induces hypothermia and glucoregulatory responses associated with nausea and torpor. Cell Reports 2024, 43: 113960. PMID: 38507407, DOI: 10.1016/j.celrep.2024.113960.Peer-Reviewed Original ResearchGlucose to lipid oxidationMetabolomics analysis of bloodImpaired insulin sensitivityRelease of stress hormonesAdipose tissue differentiationAnalysis of bloodGlucose uptakeVisceral fatChronic activationAcute activationGlucose toleranceMetabolomic analysisTranscriptome of muscleObesity treatmentTorpor-like stateNeuronal activityCell-specific activityInsulin sensitivityNauseaMetformin effectsHypothermiaWeight lossNeuronsEnergy homeostasisAugmented glucose uptake
2023
1632-P: Effects of MTOR Signaling in Muscle-Specific Irs1/2 Knockout Mice
STOEHR O, COPPS K, TAO R, WHITE M. 1632-P: Effects of MTOR Signaling in Muscle-Specific Irs1/2 Knockout Mice. Diabetes 2023, 72 DOI: 10.2337/db23-1632-p.Peer-Reviewed Original ResearchMTKO miceGlucose uptakeMTOR pathwayMdKO miceReduced ejection fractionCardiac fatty acid uptakeHigh-fat dietInsulin-resistant heartMuscle glucose uptakeDays of lifeWhite adipose tissueCardiac glucose uptakeFatty acid uptakeEffects of mTORInsulin-stimulated conditionsEjection fractionFat dietFat massMuscle atrophyIRS2 expressionCardiac hypertrophyEarly deathCardiac energyKnockout miceAdipose tissueAlternative glucose uptake mediated by β-catenin/RSK1 axis under stress stimuli in mammalian cells
Wang C, Lin R, Qi X, Xu Q, Sun X, Zhao Y, Jiang T, Jiang J, Sun Y, Deng Y, Wen J. Alternative glucose uptake mediated by β-catenin/RSK1 axis under stress stimuli in mammalian cells. Biochemical Pharmacology 2023, 214: 115645. PMID: 37321415, DOI: 10.1016/j.bcp.2023.115645.Peer-Reviewed Original ResearchConceptsPhosphorylation of TBC1D4Glucose uptakeGlucose transportActivation of RSK1Stress conditionsMechanism of glucose uptakeTranslocation of GLUT4Translocation of glucose transportersGlucose transporter translocationStress stimuliIncreased glucose uptakeB-cateninGlucose starvationEfficiency of glucose uptakeProtein complexesMammalian cellsScaffold proteinStress signalsCellular energy utilizationFamily 4TBC1D4Kinase activityRSK1Cellular adaptationCellular membranesEffects of short-term endurance and strength exercise in the molecular regulation of skeletal muscle in hyperinsulinemic and hyperglycemic Slc2a4+/− mice
Muñoz V, Botezelli J, Gaspar R, da Rocha A, Vieira R, Crisol B, Braga R, Severino M, Nakandakari S, Antunes G, Brunetto S, Ramos C, Velloso L, Simabuco F, de Moura L, da Silva A, Ropelle E, Cintra D, Pauli J. Effects of short-term endurance and strength exercise in the molecular regulation of skeletal muscle in hyperinsulinemic and hyperglycemic Slc2a4+/− mice. Cellular And Molecular Life Sciences 2023, 80: 122. PMID: 37052684, PMCID: PMC11072257, DOI: 10.1007/s00018-023-04771-2.Peer-Reviewed Original ResearchConceptsWhole-body glucose homeostasisSkeletal muscle glucose uptakeMuscle glucose uptakeMitochondrial adaptationsMitochondrial activityPost-translational mechanismsSkeletal muscleGlucose uptakeC2C12 cell lineInsulin resistanceStrength exercisesGlucose homeostasisMouse modelPhysical exerciseProtein response markersShort-term physical activityMolecular regulationTranscriptomic modulationRNA sequencingImpact of hyperglycemiaC2C12 cellsStrength exercise trainingType 2 diabetesStrength training protocolsMitochondrial functionSpatiotemporal Heterogeneity of De Novo Lipogenesis in Fixed and Living Single Cells
Shuster S, Burke M, Davis C. Spatiotemporal Heterogeneity of De Novo Lipogenesis in Fixed and Living Single Cells. The Journal Of Physical Chemistry B 2023, 127: 2918-2926. PMID: 36976708, PMCID: PMC12203757, DOI: 10.1021/acs.jpcb.2c08812.Peer-Reviewed Original ResearchConceptsDe novo lipogenesisPanc1 pancreatic cancer cellsPancreatic cancer cellsLipid dropletsType II diabetesGlucose metabolismNovo lipogenesisII diabetesLipid droplet morphologyLiver tissueGlucose uptakeCancer cellsAdipocyte cellsHigh rateLipogenesisDNL ratesCritical metabolic processesAdipocytesMajority of lipidsCellsLipidsBetter preservationObesityDiabetesTriglycerides
2022
Ubiquitin-like processing of TUG proteins as a mechanism to regulate glucose uptake and energy metabolism in fat and muscle
Bogan JS. Ubiquitin-like processing of TUG proteins as a mechanism to regulate glucose uptake and energy metabolism in fat and muscle. Frontiers In Endocrinology 2022, 13: 1019405. PMID: 36246906, PMCID: PMC9556833, DOI: 10.3389/fendo.2022.1019405.Peer-Reviewed Original ResearchConceptsGolgi matrixTUG ProteinVesicle cargoC-terminal productInsulin stimulationN-degron pathwayGLUT4 storage vesiclesCell surfaceUbiquitin-like proteinGLUT4 glucose transportersGlucose uptakeAspects of physiologyN-terminal cleavage productMuscle cellsP97 ATPaseCleavage productsC-terminusFatty acid oxidationGene expressionSingle proteinN-terminusMatrix proteinsEndoproteolytic cleavageCell typesGlucose transporterInhibitors of RNA and protein synthesis cause Glut4 translocation and increase glucose uptake in adipocytes
Meriin AB, Zaarur N, Bogan JS, Kandror KV. Inhibitors of RNA and protein synthesis cause Glut4 translocation and increase glucose uptake in adipocytes. Scientific Reports 2022, 12: 15640. PMID: 36123369, PMCID: PMC9485115, DOI: 10.1038/s41598-022-19534-5.Peer-Reviewed Original ResearchConceptsInhibitors of RNAGLUT4 translocationProtein synthesisEndocytosis of GLUT4Glucose uptakeRecycling of transferrinGlucose transporter 4Actinomycin DBiosynthesis de novoSignaling proteinsPlasma membraneTransporter 4Intracellular retentionContinuous RNATranslocationRNADe novoAdipocytesVesiclesInhibitorsTBC1D4UptakeEndocytosisGLUT4ExocytosisA precision medicine approach to metabolic therapy for breast cancer in mice
Akingbesote ND, Norman A, Zhu W, Halberstam AA, Zhang X, Foldi J, Lustberg MB, Perry RJ. A precision medicine approach to metabolic therapy for breast cancer in mice. Communications Biology 2022, 5: 478. PMID: 35595952, PMCID: PMC9122928, DOI: 10.1038/s42003-022-03422-9.Peer-Reviewed Original ResearchConceptsPrecision medicine approachBreast cancerSodium-glucose transport protein 2 inhibitorsBreast tumorsMedicine approachCanonical insulinSGLT2 inhibitor dapagliflozinEfficacy of paclitaxelBreast tumor-bearing miceTumor glucose uptakeTumor-bearing miceChemotherapy correlatesNeoadjuvant approachNeoadjuvant settingPaclitaxel chemotherapyInhibitor dapagliflozinSGLT2 inhibitorsProlonging survivalAntihyperglycemic drugsPotential adjuvantMetabolic therapyDapagliflozinTumorsDriver mutationsGlucose uptakeMultimodal analysis suggests differential immuno-metabolic crosstalk in lung squamous cell carcinoma and adenocarcinoma
Leitner BP, Givechian KB, Ospanova S, Beisenbayeva A, Politi K, Perry RJ. Multimodal analysis suggests differential immuno-metabolic crosstalk in lung squamous cell carcinoma and adenocarcinoma. Npj Precision Oncology 2022, 6: 8. PMID: 35087143, PMCID: PMC8795406, DOI: 10.1038/s41698-021-00248-2.Peer-Reviewed Original ResearchNon-small cell lung cancerLung squamous cell carcinomaBody mass indexSquamous cell carcinomaLung adenocarcinomaHigher glucose uptakeVisceral adiposityVisceral fatCell carcinomaLung cancerGlucose uptakeTreatment of NSCLCHigher Body Mass IndexTumor-infiltrating T cellsImmune checkpoint inhibitionCell lung cancerHigh visceral fatPET/CT imagingTumors of patientsPrecision therapy approachesTumor glucose uptakePrecision medicine approachLUSC tumorsPrognostic gene expressionAdjunct therapy
2021
Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis
Jiang Z, Zhao M, Voilquin L, Jung Y, Aikio MA, Sahai T, Dou FY, Roche AM, Carcamo-Orive I, Knowles JW, Wabitsch M, Appel EA, Maikawa CL, Camporez JP, Shulman GI, Tsai L, Rosen ED, Gardner CD, Spiegelman BM, Svensson KJ. Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis. Cell Metabolism 2021, 33: 1836-1852.e11. PMID: 34348115, PMCID: PMC8429235, DOI: 10.1016/j.cmet.2021.07.010.Peer-Reviewed Original ResearchConceptsFatty liver diseaseAdipose glucose uptakeGlucose toleranceLiver diseaseHepatic steatosisGlucose uptakeDiet-induced obese miceImpaired glucose toleranceInsulin-like growth factor receptorType 2 diabetesHepatic lipid synthesisIsthmin 1Growth factor receptorObese miceInsulin sensitivityTherapeutic dosingMouse modelGlucoregulatory functionGlucose regulationUnmet needTherapeutic potentialDiabetesLipid accumulationPI3K-AktFactor receptorProtein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer
Mirzapoiazova T, Xiao G, Mambetsariev B, Nasser MW, Miaou E, Singhal SS, Srivastava S, Mambetsariev I, Nelson MS, Nam A, Behal A, Arvanitis LD, Atri P, Muschen M, Tissot FLH, Miser J, Kovach JS, Sattler M, Batra SK, Kulkarni P, Salgia R. Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer. Molecular Cancer Therapeutics 2021, 20: 1820-1835. PMID: 34253596, PMCID: PMC8722383, DOI: 10.1158/1535-7163.mct-21-0013.Peer-Reviewed Original ResearchConceptsProtein phosphatase 2APhosphatase 2ASerine/threonine phosphataseDNA damage responseRegulation of apoptosisSmall molecule inhibitorsGlycolytic ATP productionThreonine phosphataseTwo-dimensional cultureLB100ATP productionMolecule inhibitorsPP2AThree-dimensional spheroid modelEndothelial cell monolayersGlucose uptakeCell viabilitySCLC cellsTherapeutic targetApoptosisCell monolayersMass spectrometrySpheroid modelTumor spheroidsCellsExercise Counterbalances Rho/ROCK2 Signaling Impairment in the Skeletal Muscle and Ameliorates Insulin Sensitivity in Obese Mice
Muñoz V, Gaspar R, Severino M, Macêdo A, Simabuco F, Ropelle E, Cintra D, da Silva A, Kim Y, Pauli J. Exercise Counterbalances Rho/ROCK2 Signaling Impairment in the Skeletal Muscle and Ameliorates Insulin Sensitivity in Obese Mice. Frontiers In Immunology 2021, 12: 702025. PMID: 34234788, PMCID: PMC8256841, DOI: 10.3389/fimmu.2021.702025.Peer-Reviewed Original ResearchConceptsSkeletal muscleInsulin receptor substrate-1Protein tyrosine phosphatase 1BSkeletal muscle glucose uptakeGlucose uptakeProtein kinase BReceptor substrate-1Muscle glucose uptakePhosphatase 1BRho kinase isoformsSubstrate-1Kinase BMolecular mechanismsSystemic glucose homeostasisTensin homologC2C12 myotubesAkt phosphorylationHigher phosphorylationMolecular analysisMuscle insulinInhibitory regulatorPotential targetRhoA-ROCK2PhosphorylationROCK2 protein281-OR: Endothelial Cell Cd36 Regulates Systemic Glucose and Lipid Metabolism
GOEDEKE L, SON N, LAMOIA T, NASIRI A, KAHN M, ZHANG X, CLINE G, GOLDBERG I, SHULMAN G. 281-OR: Endothelial Cell Cd36 Regulates Systemic Glucose and Lipid Metabolism. Diabetes 2021, 70 DOI: 10.2337/db21-281-or.Peer-Reviewed Original ResearchFatty acid uptakeLong-chain fatty acid uptakeAcid uptakeEndothelial cell CD36EC-specific deletionDifferent cell typesInsulin-stimulated glucose uptakeLipid metabolismWhole-body glucose toleranceTransmembrane proteinTissue fatty acid uptakeWhole-body insulin sensitivityEndothelial cellsHepatic glucose productionCell typesInsulin sensitivityGlucose transportSystemic glucoseSkeletal muscleCD36Glucose uptakeWhole-body fat utilizationGlucose productionSynthase fluxNon-esterified fatty acid levels
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