2020
Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance
He F, Huang Y, Song Z, Zhou HJ, Zhang H, Perry RJ, Shulman GI, Min W. Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance. Journal Of Experimental Medicine 2020, 218: e20201416. PMID: 33315085, PMCID: PMC7927432, DOI: 10.1084/jem.20201416.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipose TissueAnimalsDiabetes Mellitus, Type 2Diet, High-FatEnergy MetabolismFatty LiverGene DeletionGene TargetingGluconeogenesisHomeostasisHumansHyperglycemiaInflammationInsulin ResistanceLipogenesisLiverMaleMice, Inbred C57BLMice, KnockoutMitochondriaMitophagyNF-kappa BOxidative StressPhenotypeReactive Oxygen SpeciesSequestosome-1 ProteinSignal TransductionThioredoxinsConceptsHepatic insulin resistanceWhite adipose tissueInsulin resistanceAdipose inflammationType 2 diabetes mellitusLipid metabolic disordersNF-κB inhibitorAdipose-specific deletionWhole-body energy homeostasisAltered fatty acid metabolismFatty acid metabolismT2DM progressionT2DM patientsDiabetes mellitusReactive oxygen species pathwayHepatic steatosisMetabolic disordersNF-κBP62/SQSTM1Adipose tissueHuman adipocytesEnergy homeostasisExcessive mitophagyOxygen species pathwayInflammationMetabolic control analysis of hepatic glycogen synthesis in vivo
Nozaki Y, Petersen MC, Zhang D, Vatner DF, Perry RJ, Abulizi A, Haedersdal S, Zhang XM, Butrico GM, Samuel VT, Mason GF, Cline GW, Petersen KF, Rothman DL, Shulman GI. Metabolic control analysis of hepatic glycogen synthesis in vivo. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 8166-8176. PMID: 32188779, PMCID: PMC7149488, DOI: 10.1073/pnas.1921694117.Peer-Reviewed Original Research
2019
The integrative biology of type 2 diabetes
Roden M, Shulman GI. The integrative biology of type 2 diabetes. Nature 2019, 576: 51-60. PMID: 31802013, DOI: 10.1038/s41586-019-1797-8.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsDiabetes Mellitus, Type 2EatingHumansHyperglycemiaInsulin ResistanceLiverConceptsType 2 diabetesInsulin resistanceFrequent metabolic disorderWhite adipose tissueRelevant animal modelsCommon underlying abnormalityAdequate substrate supplyInflammatory pathwaysUnderlying abnormalityMetabolic disordersAnimal modelsAdipose tissueEnergy intakeHepatic gluconeogenesisDiabetesObesityAbnormalitiesTissue communicationRecent studiesEnergy imbalanceDysfunctionPathwayInsulinIntakeBrainAdipsin preserves beta cells in diabetic mice and associates with protection from type 2 diabetes in humans
Gómez-Banoy N, Guseh JS, Li G, Rubio-Navarro A, Chen T, Poirier B, Putzel G, Rosselot C, Pabón MA, Camporez JP, Bhambhani V, Hwang SJ, Yao C, Perry RJ, Mukherjee S, Larson MG, Levy D, Dow LE, Shulman GI, Dephoure N, Garcia-Ocana A, Hao M, Spiegelman BM, Ho JE, Lo JC. Adipsin preserves beta cells in diabetic mice and associates with protection from type 2 diabetes in humans. Nature Medicine 2019, 25: 1739-1747. PMID: 31700183, PMCID: PMC7256970, DOI: 10.1038/s41591-019-0610-4.Peer-Reviewed Original ResearchConceptsType 2 diabetesBody mass indexBeta cellsDiabetic miceInsulin secretagoguesDiabetic db/db miceDb/db micePancreatic beta-cell massBeta cell healthBeta-cell failureBeta-cell lossBeta-cell massComplement components C3aMiddle-aged adultsHuman islet cellsAlternative complement pathwayComplement factor DFuture diabetesMass indexInsulin levelsDb miceInsulin resistanceLower riskType 2Cell loss
2014
Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease
Shulman GI. Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease. New England Journal Of Medicine 2014, 371: 1131-1141. PMID: 25229917, DOI: 10.1056/nejmra1011035.Peer-Reviewed Original ResearchThe role of hepatic lipids in hepatic insulin resistance and type 2 diabetes
Perry RJ, Samuel VT, Petersen KF, Shulman GI. The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature 2014, 510: 84-91. PMID: 24899308, PMCID: PMC4489847, DOI: 10.1038/nature13478.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsType 2 diabetesHepatic insulin resistanceNon-alcoholic fatty liver diseaseFatty liver diseaseInsulin resistanceLiver diseaseHepatic lipidsHealth care costsInflammatory signalingTherapeutic approachesMortality rateDiabetesRelated epidemicsProtein kinase CεDiseaseCellular modificationsEpidemicLipid speciesMorbidityLipidsDiacylglycerol activationMice
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 Research
2001
Glucose toxicity and the development of diabetes in mice with muscle-specific inactivation of GLUT4
Kim J, Zisman A, Fillmore J, Peroni O, Kotani K, Perret P, Zong H, Dong J, Kahn C, Kahn B, Shulman G. Glucose toxicity and the development of diabetes in mice with muscle-specific inactivation of GLUT4. Journal Of Clinical Investigation 2001, 108: 153-160. PMID: 11435467, PMCID: PMC353719, DOI: 10.1172/jci10294.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAge of OnsetAnimalsDepression, ChemicalDiabetes Mellitus, Type 2Disease Models, AnimalGlucoseGlucose Transporter Type 4HyperglycemiaInsulinInsulin Infusion SystemsInsulin ResistanceKidney TubulesLiverMaleMiceMice, KnockoutMonosaccharide Transport ProteinsMuscle ProteinsMuscle, SkeletalPhlorhizinPrediabetic StateProtein TransportConceptsDevelopment of diabetesMuscle glucose uptakeKO miceHepatic glucose productionInsulin-stimulated glucose uptakeGlucose toxicityMuscle-specific inactivationGlucose uptakeAdipose tissueInsulin-stimulated muscle glucose uptakeGlucose productionWhole-body glucose uptakeSkeletal muscle glucose uptakeAdipose tissue glucose uptakeSuppress hepatic glucose productionTissue glucose uptakeHyperinsulinemic-euglycemic clampMuscle glucose transportInsulin resistanceTransgenic miceDiabetes phenotypeInsulin actionPhloridzin treatmentInsulin's abilityDiabetesUncoupling Protein-2 Negatively Regulates Insulin Secretion and Is a Major Link between Obesity, β Cell Dysfunction, and Type 2 Diabetes
Zhang C, Baffy G, Perret P, Krauss S, Peroni O, Grujic D, Hagen T, Vidal-Puig A, Boss O, Kim Y, Zheng X, Wheeler M, Shulman G, Chan C, Lowell B. Uncoupling Protein-2 Negatively Regulates Insulin Secretion and Is a Major Link between Obesity, β Cell Dysfunction, and Type 2 Diabetes. Cell 2001, 105: 745-755. PMID: 11440717, DOI: 10.1016/s0092-8674(01)00378-6.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBlood GlucoseBody WeightDiabetes MellitusDiabetes Mellitus, Type 2Disease Models, AnimalGene TargetingHomeostasisHumansHyperglycemiaInsulinInsulin SecretionIon ChannelsIslets of LangerhansMaleMembrane Transport ProteinsMiceMice, KnockoutMice, ObeseMitochondrial ProteinsModels, BiologicalObesityProteinsRNA, MessengerThermogenesisUncoupling AgentsUncoupling Protein 2ConceptsOb/ob miceInsulin secretionOb miceCell dysfunctionFirst-phase insulin secretionIslet ATP levelsGlucose-stimulated insulin secretionLevel of glycemiaSerum insulin levelsBeta-cell dysfunctionType 2 diabetesObesity-induced diabetesΒ-cell dysfunctionBeta-cell glucose sensingProtein 2UCP2-deficient miceInsulin levelsPathophysiologic significanceBeta cellsType 2SecretionMiceObesityATP levelsDiabetes
2000
Regulation of myocardial [13C]glucose metabolism in conscious rats
McNulty P, Cline G, Whiting J, Shulman G. Regulation of myocardial [13C]glucose metabolism in conscious rats. AJP Heart And Circulatory Physiology 2000, 279: h375-h381. PMID: 10899078, DOI: 10.1152/ajpheart.2000.279.1.h375.Peer-Reviewed Original Research
1999
Impaired Glucose Transport as a Cause of Decreased Insulin-Stimulated Muscle Glycogen Synthesis in Type 2 Diabetes
Cline G, Petersen K, Krssak M, Shen J, Hundal R, Trajanoski Z, Inzucchi S, Dresner A, Rothman D, Shulman G. Impaired Glucose Transport as a Cause of Decreased Insulin-Stimulated Muscle Glycogen Synthesis in Type 2 Diabetes. New England Journal Of Medicine 1999, 341: 240-246. PMID: 10413736, DOI: 10.1056/nejm199907223410404.Peer-Reviewed Original ResearchConceptsMuscle glycogen synthesisType 2 diabetes mellitusConcentrations of insulinNormal subjectsDiabetes mellitusGlucose metabolismGlycogen synthesisGlucose concentrationWhole-body glucose metabolismInsulin-stimulated muscle glycogen synthesisIntracellular glucose concentrationType 2 diabetesPlasma insulin concentrationGlucose transportImpaired glucose transportInterstitial fluid glucose concentrationsOpen-flow microperfusionIntramuscular glucoseInterstitial fluidGlucose-6-phosphate concentrationInsulin resistanceVivo microdialysisInsulin concentrationsHyperinsulinemic conditionsPatients
1998
A novel 13C NMR method to assess intracellular glucose concentration in muscle, in vivo
Cline G, Jucker B, Trajanoski Z, Rennings A, Shulman G. A novel 13C NMR method to assess intracellular glucose concentration in muscle, in vivo. American Journal Of Physiology 1998, 274: e381-e389. PMID: 9486172, DOI: 10.1152/ajpendo.1998.274.2.e381.Peer-Reviewed Original Research
1980
Effect of hyperglycemia independent of changes in insulin or glucagon on lipolysis in the conscious dog
Shulman G, Williams P, Liljenquist J, Lacy W, Keller U, Cherrington A. Effect of hyperglycemia independent of changes in insulin or glucagon on lipolysis in the conscious dog. Metabolism 1980, 29: 317-320. PMID: 6103495, DOI: 10.1016/0026-0495(80)90004-9.Peer-Reviewed Original ResearchConceptsArterial plasma glucose concentrationDirect antilipolytic effectHepatic glycerol uptakeFree fatty acid concentrationsInfusion of somatostatinContinuous glucose infusionPlasma glucose concentrationBlood glycerol levelsHyperglycemia independentConscious dogsBlood glycerolFatty acid concentrationsPancreatic hormonesAntilipolytic effectGlucose infusionBasal levelsSignificant decreaseGlycerol levelsGlucose concentrationHyperglycemiaInfusionGlucagonInsulinFractional extraction