2022
Deletion of Jazf1 gene causes early growth retardation and insulin resistance in mice
Lee H, Jang H, Li H, Samuel V, Dudek K, Osipovich A, Magnuson M, Sklar J, Shulman G. Deletion of Jazf1 gene causes early growth retardation and insulin resistance in mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2213628119. PMID: 36442127, PMCID: PMC9894197, DOI: 10.1073/pnas.2213628119.Peer-Reviewed Original ResearchConceptsKO miceEarly growth retardationInsulin resistanceFat massGrowth retardationAge-matched wild-type miceHepatic nuclear factor 4 alphaGH-IGF-1 axisHigh-fat diet feedingKO liversHyperinsulinemic-euglycemic clamp techniquePlasma growth hormone concentrationInsulin-like growth factor-1Type 2 diabetesGrowth hormone concentrationsIGF-1 expressionWild-type miceLean body massMuscle insulin resistanceGrowth factor-1Nuclear factor 4 alphaInsulin sensitivityDiet feedingPlasma concentrationsHormone concentrations
2021
Short-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
2019
Adipose 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 cagesSteatosis
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 contentMicePEPCK1 Antisense Oligonucleotide Prevents Adiposity and Impairs Hepatic Glycogen Synthesis in High-Fat Male Fed Rats
Beddow SA, Gattu AK, Vatner DF, Paolella L, Alqarzaee A, Tashkandi N, Popov V, Church C, Rodeheffer M, Cline G, Geisler J, Bhanot S, Samuel VT. PEPCK1 Antisense Oligonucleotide Prevents Adiposity and Impairs Hepatic Glycogen Synthesis in High-Fat Male Fed Rats. Endocrinology 2018, 160: 205-219. PMID: 30445425, PMCID: PMC6307100, DOI: 10.1210/en.2018-00630.Peer-Reviewed Original ResearchMeSH KeywordsAdipose Tissue, WhiteAdiposityAnimalsDiabetes Mellitus, Type 2Diet, High-FatGlucokinaseHumansInsulinIntracellular Signaling Peptides and ProteinsLipogenesisLiverLiver GlycogenMaleMiceMice, Inbred C57BLOligonucleotides, AntisensePhosphoenolpyruvate Carboxykinase (GTP)RatsRats, Sprague-DawleyConceptsHepatic glycogen synthesisAdipose tissueAntisense oligonucleotideType 2 diabetes mellitusWhite adipose tissue massIncreased hepatic gluconeogenesisChow fed ratsHepatic insulin sensitivityMale Sprague-DawleyAdipose tissue massHepatic insulin resistanceWhite adipose tissueHepatic glucose productionDe novo lipogenesisHepatic glucokinase expressionControl antisense oligonucleotideGlycogen synthesisTranscription factor 3HFF ratsDiabetes mellitusHepatic steatosisInsulin resistanceHyperglycemic clampPlasma glucoseInsulin sensitivityAngptl8 antisense oligonucleotide improves adipose lipid metabolism and prevents diet-induced NAFLD and hepatic insulin resistance in rodents
Vatner DF, Goedeke L, Camporez JG, Lyu K, Nasiri AR, Zhang D, Bhanot S, Murray SF, Still CD, Gerhard GS, Shulman GI, Samuel VT. Angptl8 antisense oligonucleotide improves adipose lipid metabolism and prevents diet-induced NAFLD and hepatic insulin resistance in rodents. Diabetologia 2018, 61: 1435-1446. PMID: 29497783, PMCID: PMC5940564, DOI: 10.1007/s00125-018-4579-1.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAngiopoietin-Like Protein 8Angiopoietin-like ProteinsAnimalsBody CompositionCalorimetry, IndirectDiet, High-FatGlucose Tolerance TestInsulin ResistanceLipid MetabolismMaleMiceMice, Inbred C57BLNon-alcoholic Fatty Liver DiseaseOligonucleotides, AntisensePeptide HormonesRatsRats, Sprague-DawleyConceptsHepatic insulin resistanceAdipose tissue lipoprotein lipaseInsulin resistanceEctopic lipid accumulationTissue lipoprotein lipaseAdipose tissueLipid uptakeTolerance testFed miceNon-alcoholic fatty liver diseaseAntisense oligonucleotideMixed meal tolerance testLipoprotein lipaseLipid accumulationDiet-induced NAFLDBariatric surgery patientsFatty liver diseaseHyperinsulinaemic euglycaemic clampMeal tolerance testSecond-generation antisense oligonucleotideAmeliorate insulin resistanceType 2 diabetesLipid-induced hepatic insulin resistanceLipoprotein lipase inhibitorWhite adipose tissue
2017
Mitochondrial 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
Insulin receptor Thr1160 phosphorylation mediates lipid-induced hepatic insulin resistance
Petersen MC, Madiraju AK, Gassaway BM, Marcel M, Nasiri AR, Butrico G, Marcucci MJ, Zhang D, Abulizi A, Zhang XM, Philbrick W, Hubbard SR, Jurczak MJ, Samuel VT, Rinehart J, Shulman GI. Insulin receptor Thr1160 phosphorylation mediates lipid-induced hepatic insulin resistance. Journal Of Clinical Investigation 2016, 126: 4361-4371. PMID: 27760050, PMCID: PMC5096902, DOI: 10.1172/jci86013.Peer-Reviewed Original ResearchConceptsInsulin receptorKinase activityHigh-fat diet-induced hepatic insulin resistanceKinase activation loopNonalcoholic fatty liver diseaseLipid-induced hepatic insulin resistanceProtein kinase CHepatic insulin resistanceDiet-induced hepatic insulin resistanceDiacylglycerol-mediated activationActivation loopPKCε inhibitionAlanine mutationsInsulin resistanceMolecular mechanismsKinase CCritical pathophysiological rolePathogenesis of T2DMechanistic linkMutantsGlycogen synthesisConsequent inhibitionPhosphorylationActive configurationPKCε
2010
Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice
Ayala JE, Consortium F, Samuel V, Morton G, Obici S, Croniger C, Shulman G, Wasserman D, McGuinness O. Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice. Disease Models & Mechanisms 2010, 3: 525-534. PMID: 20713647, PMCID: PMC2938392, DOI: 10.1242/dmm.006239.Peer-Reviewed Original ResearchDeletion of the α-Arrestin Protein Txnip in Mice Promotes Adiposity and Adipogenesis While Preserving Insulin Sensitivity
Chutkow WA, Birkenfeld AL, Brown JD, Lee HY, Frederick DW, Yoshioka J, Patwari P, Kursawe R, Cushman SW, Plutzky J, Shulman GI, Samuel VT, Lee RT. Deletion of the α-Arrestin Protein Txnip in Mice Promotes Adiposity and Adipogenesis While Preserving Insulin Sensitivity. Diabetes 2010, 59: 1424-1434. PMID: 20299477, PMCID: PMC2874703, DOI: 10.2337/db09-1212.Peer-Reviewed Original ResearchConceptsTxnip knockout miceInsulin resistanceInsulin sensitivityKnockout miceInsulin responsivenessTXNIP expressionSkeletal muscleWild-type littermate control miceStandard chow dietType 2 diabetes pathogenesisHigh-fat dietHigh-fat feedingLittermate control miceGene-deleted miceInhibits glucose uptakeControl miceChow dietAdipose massMore insulinCaloric excessFat massDiabetes pathogenesisMouse embryonic fibroblastsRegulator of adipogenesisPPARgamma expression
2001
Disruption of Sur2-containing KATP channels enhances insulin-stimulated glucose uptake in skeletal muscle
Chutkow W, Samuel V, Hansen P, Pu J, Valdivia C, Makielski J, Burant C. Disruption of Sur2-containing KATP channels enhances insulin-stimulated glucose uptake in skeletal muscle. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 11760-11764. PMID: 11562480, PMCID: PMC58803, DOI: 10.1073/pnas.201390398.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsATP-Binding Cassette TransportersBiological TransportBlood GlucoseDeoxyglucoseExonsGlucoseGlucose Clamp TechniqueGlucose Tolerance TestGlucose Transporter Type 4InsulinIntronsMiceMice, KnockoutMonosaccharide Transport ProteinsMuscle ProteinsMuscle, SkeletalPolymerase Chain ReactionPotassium ChannelsPotassium Channels, Inwardly RectifyingReceptors, DrugRNA, MessengerSignal TransductionSodium-Potassium-Exchanging ATPaseSulfonylurea ReceptorsTriglyceridesWeight GainConceptsSkeletal muscleInsulin-stimulated glucose transportGene-targeting strategiesGlucose uptake mechanismsInsulin-stimulated glucose uptakeHomozygous null miceRegulatory subunitInsertional mutagenesisWild typeEnhanced glucose useProtection of tissuesDiverse arrayGlucose transportChannel activityUptake mechanismNull miceATP-sensitive potassium channelsPotassium channelsGlucose uptakeMembrane excitabilityFuture therapeutic approachesWild-type littermatesTarget blood glucose levelsInsulin actionPhysiologic function