2024
Sustained 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 CRThe mouse metabolic phenotyping center (MMPC) live consortium: an NIH resource for in vivo characterization of mouse models of diabetes and obesity
Laughlin M, McIndoe R, Adams S, Araiza R, Ayala J, Kennedy L, Lanoue L, Lantier L, Macy J, Malabanan E, McGuinness O, Perry R, Port D, Qi N, Elias C, Shulman G, Wasserman D, Lloyd K. The mouse metabolic phenotyping center (MMPC) live consortium: an NIH resource for in vivo characterization of mouse models of diabetes and obesity. Mammalian Genome 2024, 35: 485-496. PMID: 39191872, PMCID: PMC11522164, DOI: 10.1007/s00335-024-10067-y.Peer-Reviewed Original ResearchMouse Metabolic Phenotyping CentersMouse model of diabetesModels of diabetesNational Institutes of HealthNational Institute for DiabetesDigestive and Kidney DiseasesBehavioral phenotyping testsRenal functionProcedure in vivoFood intakeIn vivo characterizationMouse modelHeterogeneity of diabetesKidney diseaseBody compositionPhenotyping CentersInstitutes of HealthMiceObesityDiabetesPhenotypic testsWhole-body carbohydrateInsulin actionLipid metabolismLiving mice
2023
FRI032 Cellular Insights Into Metabolically Healthy And Unhealthy Obesity
Petersen M, Smith G, Yu J, Barve R, Yoshino J, Shulman G, Klein S. FRI032 Cellular Insights Into Metabolically Healthy And Unhealthy Obesity. Journal Of The Endocrine Society 2023, 7: bvad114.043. PMCID: PMC10555440, DOI: 10.1210/jendso/bvad114.043.Peer-Reviewed Original ResearchAbdominal subcutaneous adipose tissueWhole-body insulin sensitivityInsulin sensitivityMUO groupMuscle ceramide contentCeramide contentAdipose tissueGreater whole-body insulin sensitivityPlasma C-peptide concentrationC-peptide concentrationsAdverse metabolic effectsSubcutaneous adipose tissueExpression of genesSkeletal muscle expressionMitochondrial content/functionHealthy obesityMitochondrial structure/functionSkeletal muscle diacylglycerolUnhealthy obesityExtracellular matrix remodelingExcess adiposityMHL groupMetabolic effectsMuscle diacylglycerolInsulin actionMAD2-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
2021
Insulin action at a molecular level – 100 years of progress
White M, Kahn C. Insulin action at a molecular level – 100 years of progress. Molecular Metabolism 2021, 52: 101304. PMID: 34274528, PMCID: PMC8551477, DOI: 10.1016/j.molmet.2021.101304.Peer-Reviewed Original ResearchConceptsAmino acid sequenceType 2 diabetesFunction of insulinAcid sequenceMolecular knowledgeHuman diseasesInsulin-sensitive tissuesPhysiological functionsPhysiological roleInsulin receptorInsulin-resistant statesInsulin 100 yearsInsulin actionBlood glucoseCascadeInsulinDiabetesTissueDiscoveryRegulationTreatmentRemarkable advancesRoleSequenceYearsInsulin sensitivity and pancreatic β-cell function in patients with primary aldosteronism
Grewal S, Fosam A, Chalk L, Deven A, Suzuki M, Correa R, Blau J, Demidowich A, Stratakis C, Muniyappa R. Insulin sensitivity and pancreatic β-cell function in patients with primary aldosteronism. Endocrine 2021, 72: 96-103. PMID: 33462741, PMCID: PMC8087621, DOI: 10.1007/s12020-020-02576-y.Peer-Reviewed Original ResearchConceptsΒ-cell functionHepatic insulin resistance indexOral glucose tolerance testPancreatic β-cell functionInsulin sensitivityInsulinogenic indexDisposition indexEffects of hyperaldosteronismCross-sectional study designInsulin resistance indexGlucose tolerance testOral disposition indexSimilar glucose toleranceBackgroundPrimary aldosteronismExcess aldosteronePA cohortArterial pressurePrimary aldosteronismGlucose toleranceControl subjectsTolerance testLess insulinResistance indexPA subjectsInsulin actionShort-term overnutrition induces white adipose tissue insulin resistance through sn-1,2-diacylglycerol – PKCε – insulin receptorT1160 phosphorylation
Lyu K, Zhang D, Song J, Li X, Perry RJ, Samuel VT, Shulman GI. Short-term overnutrition induces white adipose tissue insulin resistance through sn-1,2-diacylglycerol – PKCε – insulin receptorT1160 phosphorylation. JCI Insight 2021, 6: e139946. PMID: 33411692, PMCID: PMC7934919, DOI: 10.1172/jci.insight.139946.Peer-Reviewed Original ResearchConceptsInsulin resistanceInsulin actionAdipose tissue insulin resistanceTissue insulin resistanceWT control miceHyperinsulinemic-euglycemic clampShort-term HFDTissue insulin actionAdipose tissue insulin actionDiet-fed ratsPotential therapeutic targetHFD feedingControl miceInsulin sensitivityTherapeutic targetLipolysis suppressionImpairs insulinHFDPKCε activationGlucose uptakeΕ activationMiceDiacylglycerol accumulationRecent evidenceProtein kinase C
2020
Acute physical exercise increases PI3K‐p110α protein content in the hypothalamus of obese mice
Gaspar R, Nakandakari S, Muñoz V, Vieira R, da Silva A, Cintra D, de Moura L, Ropelle E, Pauli J. Acute physical exercise increases PI3K‐p110α protein content in the hypothalamus of obese mice. Journal Of Anatomy 2020, 238: 743-750. PMID: 33094520, PMCID: PMC7855078, DOI: 10.1111/joa.13342.Peer-Reviewed Original ResearchConceptsObese miceAcute exerciseFood intakePhysical exerciseCumulative food intakeBlood-brain barrierAcute physical exerciseEnergy homeostasis controlSuppressor of cytokineMain adipokinesHypothalamic nucleiPeripheral organsObese animalsLeptin signalingHypothalamusInsulin actionCentral signalingLeptinProtein levelsActivation of phosphoinositideMiceInsulin pathwayExerciseIntakeHomeostasis controlDietary Regulation of Immunity
Lee AH, Dixit VD. Dietary Regulation of Immunity. Immunity 2020, 53: 510-523. PMID: 32937152, PMCID: PMC7491384, DOI: 10.1016/j.immuni.2020.08.013.Peer-Reviewed Original ResearchConceptsDietary intakeOrganismal metabolismRestoration of homeostasisRegulation of glucoseMacronutrient intakeImmune regulationImmunological functionsImmunological responseImmunometabolic responsesMitochondrial respirationImmune systemInsulin actionDietary regulationProtein metabolismTissue functionIntakeDietary surplusRegulationVital functionsImmunityMetabolismHealthspanLeukocytesCheckpointHomeostasisCentral nervous pathways of insulin action in the control of metabolism and food intake
Kullmann S, Kleinridders A, Small DM, Fritsche A, Häring HU, Preissl H, Heni M. Central nervous pathways of insulin action in the control of metabolism and food intake. The Lancet Diabetes & Endocrinology 2020, 8: 524-534. PMID: 32445739, DOI: 10.1016/s2213-8587(20)30113-3.Peer-Reviewed Original ResearchConceptsPalatable food cuesCentral insulin actionCurrent findingsInsulin actionCognitive controlFood cuesCognitive healthPeripheral metabolismFood intakeMesocorticolimbic circuitryBrain insulin actionWhole-body insulin sensitivityCentral nervous pathwaysType 2 diabetesHuman researchCognitive diseasesEndogenous glucose productionDopamine systemNervous pathwaysTherapeutic optionsInsulin sensitivitySystemic metabolismAnimal modelsGlucose productionControl of metabolism
2019
282-LB: Dysregulated FGF21 Links Hepatic Insulin Resistance to Dysfunctional BAT
STOEHR O, TAO R, COPPS K, WHITE M. 282-LB: Dysregulated FGF21 Links Hepatic Insulin Resistance to Dysfunctional BAT. Diabetes 2019, 68 DOI: 10.2337/db19-282-lb.Peer-Reviewed Original ResearchHepatic insulin resistanceFGF-21Insulin resistanceHFD feedingControl miceDiabetic phenotypeGlucose metabolismFGF-21 serum levelsWhole-body glucose metabolismGlucose uptakeInsulin-resistant liverImproved glucose toleranceWild-type miceHepatic glucose productionSevere diabetic phenotypeNormal glucose uptakeHealthy batsBAT dysfunctionSerum levelsGlucose toleranceBAT functionType miceNormal rangeInsulin actionAdenoviral infection266-OR: Plasma Membrane sn-1,2 Diacylglycerol Mediates Lipid-Induced Hepatic Insulin Resistance
LYU K, ZHANG Y, ZHANG D, KAHN M, NOZAKI Y, BHANOT S, BOGAN J, CLINE G, SAMUEL V, SHULMAN G. 266-OR: Plasma Membrane sn-1,2 Diacylglycerol Mediates Lipid-Induced Hepatic Insulin Resistance. Diabetes 2019, 68 DOI: 10.2337/db19-266-or.Peer-Reviewed Original ResearchHepatic insulin resistanceInsulin resistanceExogenous fatty acidsInsulin actionLipid dropletsHepatic ceramide contentHyperinsulinemic-euglycemic clampHepatic insulin actionBioactive lipid speciesHepatic glucose productionChow-fed ratsHepatic diacylglycerol contentAdvisory PanelFatty acidsHepatic steatosisImpaired suppressionSingle doseSpouse/partnerGlucose productionPKCε activationJanssen ResearchAcute knockdownCeramide contentNational InstituteReceptor kinase activationAdipose glucocorticoid action influences whole‐body metabolism via modulation of hepatic insulin action
Abulizi A, Camporez JP, Jurczak MJ, Høyer KF, Zhang D, Cline GW, Samuel VT, Shulman GI, Vatner DF. Adipose glucocorticoid action influences whole‐body metabolism via modulation of hepatic insulin action. The FASEB Journal 2019, 33: 8174-8185. PMID: 30922125, PMCID: PMC6593882, DOI: 10.1096/fj.201802706r.Peer-Reviewed Original ResearchConceptsWhole-body metabolismHepatic insulin actionHepatic insulin resistanceGlucocorticoid actionHepatic steatosisHepatic glycogen synthesisInsulin resistanceAdipose lipolysisFood intakeInsulin actionAdipose triglyceride lipase expressionGlucose-dependent organsReceptor knockout miceOral glucose challengeHepatic lipid accumulationHigh-fat dietHyperinsulinemic-euglycemic conditionsGlycogen synthesisProtein kinase B phosphorylationInsulin responseGlucose challengeHepatic insulin responseHepatic insulinMetabolic cagesSteatosisShort-term Resistance Training Increases APPL1 Content in the Liver and the Insulin Sensitivity of Mice Fed a Long-term High-fat Diet
Minuzzi L, Kuga G, Breda L, Gaspar R, Muñoz V, Pereira R, Botezelli J, da Silva A, Cintra D, de Moura L, Ropelle E, Pauli J. Short-term Resistance Training Increases APPL1 Content in the Liver and the Insulin Sensitivity of Mice Fed a Long-term High-fat Diet. Experimental And Clinical Endocrinology & Diabetes 2019, 128: 30-37. PMID: 30991419, DOI: 10.1055/a-0885-9872.Peer-Reviewed Original ResearchConceptsLong-term high-fat dietShort-term resistance trainingHigh-fat dietResistance trainingInsulin sensitivityHigh calorie intakeLiver of miceAdiponectin pathwayChow dietMice fedInsulin resistanceGlycemic homeostasisSwiss miceAdiponectin receptorsPhysical activityPhysical exerciseInsulin actionHepatic tissueMiceLiverDietAdiponectinInadequate levelsAdverse consequencesCritical regulator
2018
Ectopic lipid deposition mediates insulin resistance in adipose specific 11β-hydroxysteroid dehydrogenase type 1 transgenic mice
Abulizi A, Camporez JP, Zhang D, Samuel VT, Shulman GI, Vatner DF. Ectopic lipid deposition mediates insulin resistance in adipose specific 11β-hydroxysteroid dehydrogenase type 1 transgenic mice. Metabolism 2018, 93: 1-9. PMID: 30576689, PMCID: PMC6401251, DOI: 10.1016/j.metabol.2018.12.003.Peer-Reviewed Original ResearchConceptsHepatic insulin resistanceEctopic lipid depositionInsulin resistanceHepatic lipid contentGlucocorticoid actionTransgenic miceLipid depositionSevere hepatic insulin resistanceTissue-specific insulin actionHepatic triglyceride contentHigh-fat dietHyperinsulinemic-euglycemic clampGlucocorticoid excessAkt serine phosphorylationGlucocorticoid activityHepatic steatosisFat dietLittermate controlsHepatic insulinInsulin actionTriglyceride contentPKCε activationDevelopment of lipidLipid contentMiceMembrane sn-1,2 Diacylglycerol Mediates Lipid-Induced Hepatic Insulin Resistance In Vivo
LYU K, ZHANG D, NOZAKI Y, ZHANG Y, BHANOT S, CLINE G, SAMUEL V, SHULMAN G. Membrane sn-1,2 Diacylglycerol Mediates Lipid-Induced Hepatic Insulin Resistance In Vivo. Diabetes 2018, 67 DOI: 10.2337/db18-243-lb.Peer-Reviewed Original ResearchHepatic insulin resistanceLipid-induced hepatic insulin resistanceDiglyceride acyltransferase 2Hepatic DAG contentInsulin resistanceHepatic insulin sensitivityInsulin sensitivityImpaired insulin-mediated suppressionActivation/translocationDGAT2 inhibitionAntisense oligonucleotideRegular chow dietInsulin-mediated suppressionHepatic insulin actionHepatic glucose productionInsulin receptor kinaseDAG contentChow dietASO treatmentIonis PharmaceuticalsInsulin actionGlucose productionPKCε activationSREBP-1cGilead SciencesKCNJ11 R201C – Neonatal Diabetes
Nally L, Wilson D. KCNJ11 R201C – Neonatal Diabetes. 2018, 61-66. DOI: 10.2337/9781580406666.case6.Peer-Reviewed Original Research
2017
Mitogen-Activated Protein Kinase Regulation in Hepatic Metabolism
Lawan A, Bennett AM. Mitogen-Activated Protein Kinase Regulation in Hepatic Metabolism. Trends In Endocrinology And Metabolism 2017, 28: 868-878. PMID: 29128158, PMCID: PMC5774993, DOI: 10.1016/j.tem.2017.10.007.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseMitogen-activated protein kinaseHepatic metabolismLipid metabolismType 2 diabetes mellitusFatty liver diseaseHepatic mitogen-activated protein kinaseHepatic metabolic functionDiabetes mellitusLiver diseaseLiver metabolismMetabolic diseasesInsulin actionPathophysiological conditionsDiseaseMetabolismMetabolic functionsRecent insightsMellitusObesityProtein kinaseMitochondrial Targeted Catalase Protects Against High-Fat Diet-Induced Muscle Insulin Resistance by Decreasing Intramuscular Lipid Accumulation
Lee HY, Lee JS, Alves T, Ladiges W, Rabinovitch PS, Jurczak MJ, Choi CS, Shulman GI, Samuel VT. Mitochondrial Targeted Catalase Protects Against High-Fat Diet-Induced Muscle Insulin Resistance by Decreasing Intramuscular Lipid Accumulation. Diabetes 2017, 66: db161334. PMID: 28476930, PMCID: PMC5521865, DOI: 10.2337/db16-1334.Peer-Reviewed Original ResearchConceptsHigh-fat dietMuscle insulin resistanceAcute lipid infusionInsulin resistanceRegular chowLipid infusionMCAT miceInsulin actionLipid-induced insulin resistanceDiet-induced insulin resistanceReactive oxygen speciesHyperinsulinemic-euglycemic clampWild-type miceMuscle fat oxidationIntramuscular lipid accumulationROS productionAcute infusionHFD-fedWT miceImpaired insulinPKCθ activationFat oxidationLipid emulsionMuscle insulinMice
2016
Tumor Necrosis Factor Inhibitors May Improve Glycemic Control in Patients Rheumatoid Arthritis and Concomitant Type 2 Diabetes Mellitus
Danve A, Division of Rheumatology Y, Sehra S, Jaykumar D, Kulkarni S, Instructor M, Internal Medicine N, Attending Physician M. Tumor Necrosis Factor Inhibitors May Improve Glycemic Control in Patients Rheumatoid Arthritis and Concomitant Type 2 Diabetes Mellitus. Osteology And Rheumatology – Open Journal 2016, 1: 17-19. DOI: 10.17140/orhoj-1-106.Peer-Reviewed Original ResearchInsulin-sensitive tissuesInsulin receptor beta-subunitInsulin receptor substrate-1Inhibit insulin signalingReceptor beta-subunitInsulin-sensitive glucose transporterType 2 diabetes mellitusPhosphorylation cascadeTransmembrane signalingInsulin signalingTNF-aBeta subunitInsulin resistancePromote insulin resistanceGlucose transportConcomitant type 2 diabetes mellitusInsulin actionSensitive tissuesTumor necrosis factor-aInterleukin (IL)-6GLUT-4Factor AReceptor antibodiesLean ratsMetabolic syndrome
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