2023
MAD2-Dependent Insulin Receptor Endocytosis Regulates Metabolic Homeostasis.
Park J, Hall C, Hubbard B, LaMoia T, Gaspar R, Nasiri A, Li F, Zhang H, Kim J, Haeusler R, Accili D, Shulman G, Yu H, Choi E. MAD2-Dependent Insulin Receptor Endocytosis Regulates Metabolic Homeostasis. Diabetes 2023, 72: 1781-1794. PMID: 37725942, PMCID: PMC10658066, DOI: 10.2337/db23-0314.Peer-Reviewed Original ResearchConceptsIR endocytosisInsulin receptor endocytosisCell division regulatorsInsulin receptorProlongs insulin actionReceptor endocytosisTranscriptomic profilesInsulin stimulationEndocytosisMetabolic homeostasisCell surfaceGenetic ablationMetabolic functionsInsulin actionP31cometMad2BubR1DisruptionSignalingRegulatorHomeostasisAdipose tissueInteractionHepatic fat accumulationMetabolism
2022
Distinct subcellular localisation of intramyocellular lipids and reduced PKCε/PKCθ activity preserve muscle insulin sensitivity in exercise-trained mice
Gaspar R, Lyu K, Hubbard B, Leitner B, Luukkonen P, Hirabara S, Sakuma I, Nasiri A, Zhang D, Kahn M, Cline G, Pauli J, Perry R, Petersen K, Shulman G. Distinct subcellular localisation of intramyocellular lipids and reduced PKCε/PKCθ activity preserve muscle insulin sensitivity in exercise-trained mice. Diabetologia 2022, 66: 567-578. PMID: 36456864, PMCID: PMC11194860, DOI: 10.1007/s00125-022-05838-8.Peer-Reviewed Original ResearchConceptsProtein kinase CsSubcellular compartmentsDistinct subcellular localisationMuscle insulin sensitivityMultiple subcellular compartmentsInsulin receptor kinaseNovel protein kinase CsActivation of PKCεSubcellular localisationPKCθ translocationReceptor kinasePlasma membraneSubcellular distributionTriacylglycerol contentCrucial pathwaysIntramuscular triacylglycerol contentRC miceDiacylglycerolConclusions/interpretationThese resultsPKCεPM compartmentPhosphorylationMuscle triacylglycerol contentSkeletal muscleRecent findingsShort-term physical exercise controls age-related hyperinsulinemia and improves hepatic metabolism in aged rodents
Muñoz V, Gaspar R, Mancini M, de Lima R, Vieira R, Crisol B, Antunes G, Trombeta J, Bonfante I, Simabuco F, da Silva A, Cavaglieri C, Ropelle E, Cintra D, Pauli J. Short-term physical exercise controls age-related hyperinsulinemia and improves hepatic metabolism in aged rodents. Journal Of Endocrinological Investigation 2022, 46: 815-827. PMID: 36318449, DOI: 10.1007/s40618-022-01947-8.Peer-Reviewed Original ResearchConceptsInsulin sensitivityHepatic metabolismPhysical exerciseInsulin resistanceAerobic exerciseMetabolic healthAged rodentsShort-term aerobic exerciseAge-related insulin resistanceShort-term exercise trainingSignificant metabolic impairmentType 2 diabetesHepatic fat accumulationWhole-body glucoseDevelopment/progressionHepatic fat metabolismExercise trainingGlucose toleranceInsulin secretionFat accumulationHigh prevalenceHyperinsulinemic ratsMetabolic impairmentElderly populationGlucose homeostasis
2021
Exercise 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 protein
2020
Physical exercise increases ROCK activity in the skeletal muscle of middle-aged rats
Muñoz V, Gaspar R, Esteca M, Baptista I, Vieira R, da Silva A, de Moura L, Cintra D, Ropelle E, Pauli J. Physical exercise increases ROCK activity in the skeletal muscle of middle-aged rats. Mechanisms Of Ageing And Development 2020, 186: 111213. PMID: 32032622, DOI: 10.1016/j.mad.2020.111213.Peer-Reviewed Original ResearchConceptsMiddle-aged ratsSoleus musclePhysical exerciseGlucose homeostasisAge-related metabolic disordersSkeletal muscle glucose uptakeSkeletal muscleImpaired glucose homeostasisType 2 diabetesMuscle glucose uptakeInsulin receptor substrate-1 phosphorylationWhole-body glucose homeostasisROCK activitySkeletal muscle fiber typesMuscle fiber typesInsulin resistanceSedentary ratsHigh insulinDifferent skeletal muscle fiber typesMetabolic disordersMetabolism-related genesPharmacological inhibitionRatsGlucose uptakeMuscle
2018
The Effects of Aging on Rho-Kinase and Insulin Signaling in Skeletal Muscle and White Adipose Tissue of Rats
Muñoz V, Gaspar R, Kuga G, Pavan I, Simabuco F, da Silva A, de Moura L, Cintra D, Ropelle E, Pauli J. The Effects of Aging on Rho-Kinase and Insulin Signaling in Skeletal Muscle and White Adipose Tissue of Rats. The Journals Of Gerontology Series A 2018, 75: 432-436. PMID: 30596894, DOI: 10.1093/gerona/gly293.Peer-Reviewed Original ResearchUnsaturated fatty acids from flaxseed oil and exercise modulate GPR120 but not GPR40 in the liver of obese mice: a new anti-inflammatory approach
Gaspar R, Veiga C, Bessi M, Dátilo M, Sant'Ana M, Rodrigues P, de Moura L, da Silva A, Santos G, Catharino R, Ropelle E, Pauli J, Cintra D. Unsaturated fatty acids from flaxseed oil and exercise modulate GPR120 but not GPR40 in the liver of obese mice: a new anti-inflammatory approach. The Journal Of Nutritional Biochemistry 2018, 66: 52-62. PMID: 30771734, DOI: 10.1016/j.jnutbio.2018.12.003.Peer-Reviewed Original ResearchConceptsHigh-fat dietPhysical exerciseObese miceNew anti-inflammatory approachesFlaxseed oilAnti-inflammatory approachesAnti-inflammatory propertiesChronic physical exerciseImpact of exerciseType 2 diabetesInflammatory markersInflammatory responseExercise performanceHepatic metabolismGPR120Fat depotsSources of ω3GPR40ObesityLiverΒ-arrestinMiceRelated cascadesExerciseInsulinPhysical training reverses changes in hepatic mitochondrial diameter of Alloxan-induced diabetic rats
Kuga G, Gaspar R, Muñoz V, Nakandakari S, Breda L, Sandoval B, Caetano F, de Almeida Leme J, Pauli J, Gomes R. Physical training reverses changes in hepatic mitochondrial diameter of Alloxan-induced diabetic rats. Einstein (São Paulo) 2018, 16: eao4353. PMID: 30088548, PMCID: PMC6110382, DOI: 10.1590/s1679-45082018ao4353.Peer-Reviewed Original ResearchConceptsDiabetic ratsBody weightDiabetic groupSedentary diabeticDiabetic animalsPhysical trainingSedentary diabetic animalsPhysical training protocolMitochondrial diameterDiabetes mellitusAlloxan administrationBlood insulinExercise protocolSerum glucoseSedentary controlsWistar ratsHepatic metabolismReverses changesLiver glycogenHepatic glycogenDiabeticsRatsMeasurements of glycogenLiver samplesTraining protocolAcute physical exercise increases the adaptor protein APPL1 in the hypothalamus of obese mice
Gaspar R, Muñoz V, Formigari G, Kuga G, Nakandakari S, Botezelli J, da Silva A, Cintra D, de Moura L, Ropelle E, Pauli J. Acute physical exercise increases the adaptor protein APPL1 in the hypothalamus of obese mice. Cytokine 2018, 110: 87-93. PMID: 29705396, DOI: 10.1016/j.cyto.2018.04.013.Peer-Reviewed Original ResearchConceptsAcute physical exerciseObese micePhysical exerciseFood intakeArcuate proopiomelanocortin neuronsSerum adiponectin levelsProtein-3 levelsEffects of leptinCentral nervous systemRole of APPL1Proopiomelanocortin neuronsAdiponectin levelsAcute exerciseNervous systemHypothalamusPathophysiological processesAdiponectinAdaptor protein APPL1MiceProtein kinase BLeucine zipper motif 1Kinase BExerciseIntakeProtein contentImpaired insulin signaling and spatial learning in middle-aged rats: The role of PTP1B
Kuga G, Muñoz V, Gaspar R, Nakandakari S, da Silva A, Botezelli J, Leme J, Gomes R, de Moura L, Cintra D, Ropelle E, Pauli J. Impaired insulin signaling and spatial learning in middle-aged rats: The role of PTP1B. Experimental Gerontology 2018, 104: 66-71. PMID: 29421605, DOI: 10.1016/j.exger.2018.02.005.Peer-Reviewed Original ResearchConceptsMiddle-aged ratsBrain-derived neurotrophic factorΒ-amyloid contentAlzheimer's diseaseInsulin resistanceTau phosphorylationMorris water maze testMiddle-aged Wistar ratsInsulin tolerance testMain risk factorsAge-related changesNeurotrophic factorTolerance testRisk factorsMaze testImpaired insulinWistar ratsNew therapiesHippocampus regionBody weightCognitive declineRole of PTP1BSynaptic plasticityRatsSpatial learningExercise increases Rho‐kinase activity and insulin signaling in skeletal muscle
Muñoz V, Gaspar R, Kuga G, da Rocha A, Crisol B, Botezelli J, Baptista I, Mekary R, da Silva A, Cintra D, de Moura L, Ropelle E, Pauli J. Exercise increases Rho‐kinase activity and insulin signaling in skeletal muscle. Journal Of Cellular Physiology 2018, 233: 4791-4800. PMID: 29219181, DOI: 10.1002/jcp.26278.Peer-Reviewed Original Research
2017
Overexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3) reduces FoxO1 phosphorylation in mice hypothalamus
de Almeida Rodrigues B, Kuga G, Muñoz V, Gaspar R, Tavares M, Botezelli J, da Silva A, Cintra D, de Moura L, Simabuco F, Ropelle E, Pauli J. Overexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3) reduces FoxO1 phosphorylation in mice hypothalamus. Neuroscience Letters 2017, 659: 14-17. PMID: 28866049, DOI: 10.1016/j.neulet.2017.08.067.Peer-Reviewed Original ResearchConceptsFoxO1 phosphorylationMKP-3 overexpressionDephosphorylation of FOXO1Potential therapeutic targetInjection of adenovirusOrexigenic neuropeptidesHypothalamic disorderHypothalamic third ventricleSwiss miceInsulin intracellularHypothalamic activationThird ventricleTherapeutic targetFoxO1 dephosphorylationAkt phosphorylationInsulin signalingImportant transcription factorDUSP6 geneHypothalamusSignificant reductionFOXO1MiceInsulin stimulationPresent studyInsulin signal