2015
Macrophage-specific de Novo Synthesis of Ceramide Is Dispensable for Inflammasome-driven Inflammation and Insulin Resistance in Obesity*
Camell CD, Nguyen KY, Jurczak MJ, Christian BE, Shulman GI, Shadel GS, Dixit VD. Macrophage-specific de Novo Synthesis of Ceramide Is Dispensable for Inflammasome-driven Inflammation and Insulin Resistance in Obesity*. Journal Of Biological Chemistry 2015, 290: 29402-29413. PMID: 26438821, PMCID: PMC4705943, DOI: 10.1074/jbc.m115.680199.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsBone Marrow CellsCarrier ProteinsCeramidesDiet, High-FatDisease Models, AnimalFatty AcidsFemaleInflammasomesInflammationInsulin ResistanceLipidsMacrophagesMaleMiceMice, TransgenicMitochondriaNLR Family, Pyrin Domain-Containing 3 ProteinObesityOxidative StressSerine C-PalmitoyltransferaseConceptsDe novo synthesisNovo synthesisOverexpression of catalaseDietary lipid overloadSynthesis machineryTissue homeostasisCell-specific deletionInflammasome activationAdipose tissue homeostasisNLRP3 inflammasome activationMyeloid cell-specific deletionMetabolic pathwaysCeramide synthesisAlternate metabolic pathwaysCaspase-1 cleavageEnergy homeostasisLipid overloadCeramideLipid metabolismInflammasome-dependent mannerOxidative stressDanger signalsFat diet-induced obesityHomeostasisFatty acids
2001
Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance
Kim J, Fillmore J, Chen Y, Yu C, Moore I, Pypaert M, Lutz E, Kako Y, Velez-Carrasco W, Goldberg I, Breslow J, Shulman G. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 7522-7527. PMID: 11390966, PMCID: PMC34701, DOI: 10.1073/pnas.121164498.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseFatty Acids, NonesterifiedGlucagonGlucoseGlucose Clamp TechniqueGlucose Tolerance TestHeterozygoteInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceLeptinLipoprotein LipaseLiverMiceMice, KnockoutMice, TransgenicMuscle, SkeletalOrgan SpecificityPhosphatidylinositol 3-KinasesPhosphoproteinsSignal TransductionTriglyceridesConceptsInsulin resistanceFatty acid-derived metabolitesInsulin actionTriglyceride contentType 2 diabetes mellitusInsulin activationLipoprotein lipaseInsulin receptor substrate-1-associated phosphatidylinositolMuscle triglyceride contentSkeletal muscleTissue-specific insulin resistanceLiver triglyceride contentAdipocyte-derived hormoneHyperinsulinemic-euglycemic clampEndogenous glucose productionLiver-specific overexpressionTissue-specific overexpressionInsulin-stimulated glucose uptakeDiabetes mellitusTissue-specific increaseTransgenic miceGlucose productionFat metabolismGlucose uptakeInsulinInsulin Resistance and a Diabetes Mellitus-Like Syndrome in Mice Lacking the Protein Kinase Akt2 (PKBβ)
Cho H, Mu J, Kim J, Thorvaldsen J, Chu Q, Crenshaw E, Kaestner K, Bartolomei M, Shulman G, Birnbaum M. Insulin Resistance and a Diabetes Mellitus-Like Syndrome in Mice Lacking the Protein Kinase Akt2 (PKBβ). Science 2001, 292: 1728-1731. PMID: 11387480, DOI: 10.1126/science.292.5522.1728.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseDeoxyglucoseDiabetes Mellitus, Type 2FemaleGene TargetingGlucoseGlucose Clamp TechniqueGlucose Tolerance TestHomeostasisInsulinInsulin ResistanceIslets of LangerhansLiverMaleMiceMice, Inbred C57BLMice, TransgenicMuscle, SkeletalProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktSignal TransductionConceptsSerine-threonine protein kinase AktProtein kinase Akt2Protein kinase AktProtein kinase B.Activation of phosphatidylinositolEssential genesKinase Akt2Kinase AktAbility of insulinGlucose homeostasisNormal glucose homeostasisAkt2Critical initial stepEarly eventsSkeletal muscleHomeostasisInsulin actionMice LackingInsulin responsivenessInitial stepActivationInsulin resistancePhosphatidylinositolBlood glucoseGenesOverexpression of the LAR (leukocyte antigen-related) protein-tyrosine phosphatase in muscle causes insulin resistance
Zabolotny J, Kim Y, Peroni O, Kim J, Pani M, Boss O, Klaman L, Kamatkar S, Shulman G, Kahn B, Neel B. Overexpression of the LAR (leukocyte antigen-related) protein-tyrosine phosphatase in muscle causes insulin resistance. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 5187-5192. PMID: 11309481, PMCID: PMC33185, DOI: 10.1073/pnas.071050398.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseBody CompositionCreatine KinaseCreatine Kinase, MM FormFatty Acids, NonesterifiedHumansInsulinInsulin ResistanceIntracellular Signaling Peptides and ProteinsIsoenzymesMiceMice, TransgenicMusclesOrgan SpecificityPhosphatidylinositol 3-KinasesPhosphorylationPhosphotyrosinePromoter Regions, GeneticProtein Tyrosine Phosphatase, Non-Receptor Type 6Protein Tyrosine PhosphatasesRecombinant Fusion ProteinsSignal TransductionConceptsIRS proteinsLAR protein tyrosine phosphataseKinase activityProtein tyrosine phosphatase LARIRS-2Insulin receptor substrate-1Protein tyrosine phosphatasePI3-kinase activityInsulin-resistant humansReceptor substrate-1Association of p85alphaInsulin resistanceInsulin-responsive tissuesHuman LARTyrosyl phosphorylationInsulin target tissuesTransgenic miceSubstrate-1IRS-1Wild-type controlsInsulin receptorWhole-body glucose disposalWhole-body insulin resistancePhosphotyrosinePhosphorylation
2000
Transgenic mice overexpressing GLUT-1 protein in muscle exhibit increased muscle glycogenesis after exercise
Ren J, Barucci N, Marshall B, Hansen P, Mueckler M, Shulman G. Transgenic mice overexpressing GLUT-1 protein in muscle exhibit increased muscle glycogenesis after exercise. AJP Endocrinology And Metabolism 2000, 278: e588-e592. PMID: 10751190, DOI: 10.1152/ajpendo.2000.278.4.e588.Peer-Reviewed Original ResearchConceptsTg miceMuscle glycogen concentrationNT miceTransgenic miceGlycogen concentrationH postexerciseEDL musclesGastrocnemius muscleMuscle glycogenExtensor digitorum longus muscleMale transgenic miceIsolated EDL musclesAge-matched littermatesDigitorum longus muscleMuscle glycogen synthase activationMuscle glycogenesisLongus muscleMuscle glycogenolysisGLUT-1 proteinSynthase activationMicePostexerciseHuman GLUT-1GLUT-1Glycogen synthase activationMechanism of Insulin Resistance in A-ZIP/F-1 Fatless Mice*
Kim J, Gavrilova O, Chen Y, Reitman M, Shulman G. Mechanism of Insulin Resistance in A-ZIP/F-1 Fatless Mice*. Journal Of Biological Chemistry 2000, 275: 8456-8460. PMID: 10722680, DOI: 10.1074/jbc.275.12.8456.Peer-Reviewed Original ResearchConceptsType 2 diabetesInsulin resistanceFatless miceInsulin actionTriglyceride contentA-ZIP/FDevelopment of diabetesLiver triglyceride contentHyperinsulinemic-euglycemic clampAccumulation of triglyceridesMuscle/liverWild-type littermatesInsulin receptor substrate-1Receptor substrate-1Partitioning of fatSubsequent impairmentDiabetesFat metabolismMiceFat tissueLiverInsulin signalingMuscleLatter tissueSubstrate-1