2019
Hepatic insulin sensitivity is improved in high‐fat diet‐fed Park2 knockout mice in association with increased hepatic AMPK activation and reduced steatosis
Edmunds LR, Huckestein BR, Kahn M, Zhang D, Chu Y, Zhang Y, Wendell SG, Shulman GI, Jurczak MJ. Hepatic insulin sensitivity is improved in high‐fat diet‐fed Park2 knockout mice in association with increased hepatic AMPK activation and reduced steatosis. Physiological Reports 2019, 7: e14281. PMID: 31724300, PMCID: PMC6854109, DOI: 10.14814/phy2.14281.Peer-Reviewed Original ResearchConceptsPark2 KO miceHepatic insulin sensitivityKO miceInsulin sensitivityInsulin resistanceShort-term HFD feedingDiet-induced hepatic insulin resistanceWhole-body insulin sensitivityPark2 knockout miceImproved hepatic insulin sensitivityDiet-induced obesityHigh-fat dietBioactive lipid speciesTumor necrosis factorHepatic insulin resistanceHepatic AMPK activationNegative energy balanceEndoplasmic reticulum stress responseRegular chowCytokine levelsHFD feedingReduced steatosisChronic HFDInterleukin-6Necrosis factor
2013
Cellular Mechanisms by Which FGF21 Improves Insulin Sensitivity in Male Mice
Camporez JP, Jornayvaz FR, Petersen MC, Pesta D, Guigni BA, Serr J, Zhang D, Kahn M, Samuel VT, Jurczak MJ, Shulman GI. Cellular Mechanisms by Which FGF21 Improves Insulin Sensitivity in Male Mice. Endocrinology 2013, 154: 3099-3109. PMID: 23766126, PMCID: PMC3749479, DOI: 10.1210/en.2013-1191.Peer-Reviewed Original ResearchMeSH KeywordsAdipose Tissue, BrownAnimalsCells, CulturedDiet, High-FatDrug ImplantsEnergy MetabolismFibroblast Growth FactorsGlucose IntoleranceHumansInfusions, SubcutaneousInsulin ResistanceIsoenzymesLipectomyLipid MetabolismLiverMaleMiceMice, Inbred C57BLMuscle, SkeletalProtein Kinase CProtein Kinase C-epsilonProtein Kinase C-thetaRecombinant ProteinsConceptsType 2 diabetesInsulin resistanceRegular chowInsulin sensitivityInsulin actionNonalcoholic fatty liver diseaseFibroblast growth factor 21Fatty liver diseasePeripheral insulin sensitivityEffects of FGF21HFD-fed miceGrowth factor 21High-fat dietCellular mechanismsWild-type miceWhite adipose tissueMuscle insulin resistanceMuscle ceramide contentProtein kinase Cε activationFGF21 administrationLiver diseaseFactor 21Male miceNovel therapiesAdipose tissueCellular Mechanism by Which Estradiol Protects Female Ovariectomized Mice From High-Fat Diet-Induced Hepatic and Muscle Insulin Resistance
Camporez JP, Jornayvaz FR, Lee HY, Kanda S, Guigni BA, Kahn M, Samuel VT, Carvalho CR, Petersen KF, Jurczak MJ, Shulman GI. Cellular Mechanism by Which Estradiol Protects Female Ovariectomized Mice From High-Fat Diet-Induced Hepatic and Muscle Insulin Resistance. Endocrinology 2013, 154: 1021-1028. PMID: 23364948, PMCID: PMC3578999, DOI: 10.1210/en.2012-1989.Peer-Reviewed Original ResearchConceptsEstrogen replacement therapyOVX miceMuscle insulin sensitivityMuscle insulin resistanceInsulin resistanceInsulin sensitivityReplacement therapyHigh-fat diet feedingWhole-body insulin resistanceWhole-body insulin sensitivityFemale ovariectomized miceEctopic lipid depositionWhole-body energy expenditureType 2 diabetesEnergy expenditureWeeks of ageWhole-body energy homeostasisProtein kinase Cε activationHepatic DAG contentLivers of shamPostmenopausal womenSham miceOvariectomized miceGlucose toleranceE2 treatmentRole of patatin‐like phospholipase domain‐containing 3 on lipid‐induced hepatic steatosis and insulin resistance in rats
Kumashiro N, Yoshimura T, Cantley JL, Majumdar SK, Guebre‐Egziabher F, Kursawe R, Vatner DF, Fat I, Kahn M, Erion DM, Zhang X, Zhang D, Manchem VP, Bhanot S, Gerhard GS, Petersen KF, Cline GW, Samuel VT, Shulman GI. Role of patatin‐like phospholipase domain‐containing 3 on lipid‐induced hepatic steatosis and insulin resistance in rats. Hepatology 2013, 57: 1763-1772. PMID: 23175050, PMCID: PMC3597437, DOI: 10.1002/hep.26170.Peer-Reviewed Original ResearchCGI-58 knockdown sequesters diacylglycerols in lipid droplets/ER-preventing diacylglycerol-mediated hepatic insulin resistance
Cantley JL, Yoshimura T, Camporez JP, Zhang D, Jornayvaz FR, Kumashiro N, Guebre-Egziabher F, Jurczak MJ, Kahn M, Guigni BA, Serr J, Hankin J, Murphy RC, Cline GW, Bhanot S, Manchem VP, Brown JM, Samuel VT, Shulman GI. CGI-58 knockdown sequesters diacylglycerols in lipid droplets/ER-preventing diacylglycerol-mediated hepatic insulin resistance. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 1869-1874. PMID: 23302688, PMCID: PMC3562813, DOI: 10.1073/pnas.1219456110.Peer-Reviewed Original ResearchMeSH Keywords1-Acylglycerol-3-Phosphate O-AcyltransferaseAdipose Tissue, WhiteAnimalsCell MembraneDiet, High-FatDiglyceridesEndoplasmic ReticulumGene ExpressionGene Knockdown TechniquesHumansImmunoblottingInjections, IntraperitonealInsulin ResistanceLipidsLiverMaleMiceMice, Inbred C57BLOligonucleotides, AntisenseProtein Kinase C-epsilonProtein TransportReverse Transcriptase Polymerase Chain ReactionConceptsHepatic insulin resistanceInsulin resistanceHepatic steatosisCGI-58 knockdownHigh-fat fed miceHyperinsulinemic-euglycemic clamp studiesSevere hepatic steatosisCGI-58 expressionFat-fed miceLipid-induced hepatic insulin resistanceChanarin-Dorfman syndromeComparative gene identification-58Lipid droplet-associated proteinAdipose triglyceride lipaseDroplet-associated proteinAntisense oligonucleotide treatmentInsulin sensitivityASO treatmentClamp studiesLipotoxic conditionsKnockdown miceCGI-58PKCε activationMiceTriglyceride lipase