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 accumulationMetabolismEffects 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 functionShort-term flaxseed oil, rich in omega 3, protects mice against metabolic damage caused by high-fat diet, but not inflammation
Nakandakari S, Gaspar R, Kuga G, Ramos C, Vieira R, Rios T, Muñoz V, Sant'ana M, Simabuco F, da Silva A, Moura L, Ropelle E, Pauli J, Cintra D. Short-term flaxseed oil, rich in omega 3, protects mice against metabolic damage caused by high-fat diet, but not inflammation. The Journal Of Nutritional Biochemistry 2023, 114: 109270. PMID: 36706930, DOI: 10.1016/j.jnutbio.2023.109270.Peer-Reviewed Original ResearchConceptsControl groupFood intakeAdipose tissueLong-term high-fat diet feedingHigh-fat diet feedingFlaxseed oilHigh-fat dietMesenteric adipose tissueFatty acid incorporationNeuronal signaling pathwaysInflammatory markersHF dietInflammatory effectsDiet feedingEarly inflammationHF groupLipid profileTNFα proteinProtective effectTriggers inflammationMetabolic disordersGlucose homeostasisBody weightInflammationHF consumption
2022
Q-Flux: A method to assess hepatic mitochondrial succinate dehydrogenase, methylmalonyl-CoA mutase, and glutaminase fluxes in vivo
Hubbard B, LaMoia T, Goedeke L, Gaspar R, Galsgaard K, Kahn M, Mason G, Shulman G. Q-Flux: A method to assess hepatic mitochondrial succinate dehydrogenase, methylmalonyl-CoA mutase, and glutaminase fluxes in vivo. Cell Metabolism 2022, 35: 212-226.e4. PMID: 36516861, PMCID: PMC9887731, DOI: 10.1016/j.cmet.2022.11.011.Peer-Reviewed Original ResearchShort-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 homeostasisMetformin, phenformin, and galegine inhibit complex IV activity and reduce glycerol-derived gluconeogenesis
LaMoia TE, Butrico GM, Kalpage HA, Goedeke L, Hubbard BT, Vatner DF, Gaspar RC, Zhang XM, Cline GW, Nakahara K, Woo S, Shimada A, Hüttemann M, Shulman GI. Metformin, phenformin, and galegine inhibit complex IV activity and reduce glycerol-derived gluconeogenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2122287119. PMID: 35238637, PMCID: PMC8916010, DOI: 10.1073/pnas.2122287119.Peer-Reviewed Original ResearchConceptsGlucose-lowering effectPlasma glucose concentrationComplex I activityHepatic gluconeogenesisType 2 diabetes mellitusGlucose concentrationGlycerol-3-phosphate dehydrogenase activityI activityDiabetes mellitusSelective inhibitionMetforminInhibitionRelevant concentrationsGluconeogenesisPhenforminVivoMost studiesDehydrogenase activityGalegineMellitus
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 proteinAn update on brown adipose tissue biology: a discussion of recent findings
Gaspar RC, Pauli JR, Shulman GI, Muñoz VR. An update on brown adipose tissue biology: a discussion of recent findings. AJP Endocrinology And Metabolism 2021, 320: e488-e495. PMID: 33459179, PMCID: PMC7988785, DOI: 10.1152/ajpendo.00310.2020.Peer-Reviewed Original ResearchConceptsBrown adipose tissueBAT thermogenesisBrown adipose tissue biologyEnergy expenditureBrown-like cellsWhole-body glucoseAdipose tissue biologyBAT metabolismAdrenergic drugsAdipose tissuePotential treatmentThermogenic activityWhite adipocytesBody glucoseFat metabolismEndocrine mechanismsBeneficial roleSecretory moleculesActivity capacityTissue biologyThermogenesisRecent findingsRecent studiesAdditional focusMetabolism
2020
Effects of short-term physical training on the interleukin-15 signalling pathway and glucose tolerance in aged rats
Minuzzi L, da Conceição L, Muñoz V, Vieira R, Gaspar R, da Silva A, Cintra D, Pereira de Moura L, Ropelle E, Teixeira A, Pauli J. Effects of short-term physical training on the interleukin-15 signalling pathway and glucose tolerance in aged rats. Cytokine 2020, 137: 155306. PMID: 33010727, DOI: 10.1016/j.cyto.2020.155306.Peer-Reviewed Original ResearchConceptsAerobic physical trainingInsulin sensitivityIL-15Physical trainingGlucose toleranceInterleukin-15Elderly ratsWhole-body insulin sensitivityShort-term physical trainingSkeletal muscleLast exercise sessionExercise training protocolMesenteric fat massPhysical exercise trainingPhysical exercise protocolSkeletal muscle alterationsFourteen Wistar ratsExpression of HIF1αExercise trainingExercise protocolExercise sessionsMuscle alterationsFat massWistar ratsSupraphysiological levelsAging is associated with increased TRB3, ER stress, and hepatic glucose production in the liver of rats
Gaspar R, Muñoz V, Nakandakari S, Vieira R, da Conceição L, de Oliveira F, Crisol B, da Silva A, Cintra D, de Moura L, Ropelle E, Zaghloul I, Mekary R, Pauli J. Aging is associated with increased TRB3, ER stress, and hepatic glucose production in the liver of rats. Experimental Gerontology 2020, 139: 111021. PMID: 32659331, DOI: 10.1016/j.exger.2020.111021.Peer-Reviewed Original ResearchConceptsER stressEukaryotic translation initiation factorProtein kinase RNA-like endoplasmic reticulum kinaseRNA-like endoplasmic reticulum kinaseTranslation initiation factorPhosphorylation of inositolStress response regulationEndoplasmic reticulum kinaseEndoplasmic reticulum stress pathwayMammalian homologDrosophila tribblesEndoplasmic reticulum stressInitiation factorsProtein contentTRB3Multiple tissuesStress pathwaysImmunoglobulin proteinEnzymes of gluconeogenesisReticulum stressHepatic glucose productionEnzyme 1Response regulationMolecular changesPyruvate challengePhysical 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
2019
Rho-kinase activity is upregulated in the skeletal muscle of aged exercised rats
Muñoz V, Gaspar R, Minuzzi L, Dos Santos Canciglieri R, da Silva A, de Moura L, Cintra D, Ropelle E, Pauli J. Rho-kinase activity is upregulated in the skeletal muscle of aged exercised rats. Experimental Gerontology 2019, 128: 110746. PMID: 31629802, DOI: 10.1016/j.exger.2019.110746.Peer-Reviewed Original Research