2020
Membrane-bound sn-1,2-diacylglycerols explain the dissociation of hepatic insulin resistance from hepatic steatosis in MTTP knockout mice
Abulizi A, Vatner DF, Ye Z, Wang Y, Camporez JP, Zhang D, Kahn M, Lyu K, Sirwi A, Cline GW, Hussain MM, Aspichueta P, Samuel VT, Shulman GI. Membrane-bound sn-1,2-diacylglycerols explain the dissociation of hepatic insulin resistance from hepatic steatosis in MTTP knockout mice. Journal Of Lipid Research 2020, 61: 1565-1576. PMID: 32907986, PMCID: PMC7707176, DOI: 10.1194/jlr.ra119000586.Peer-Reviewed Original ResearchConceptsHepatic insulin resistanceInsulin resistanceHepatic insulin sensitivityHepatic steatosisLipid-induced hepatic insulin resistancePKCε activationInsulin sensitivityKnockout miceNormal hepatic insulin sensitivityWild-type control miceHepatic ceramide contentHyperinsulinemic-euglycemic clampComprehensive metabolic phenotypingLipid dropletsHepatic DAG contentDAG contentGlucose intoleranceControl miceMTTP activityHepatic insulinAnimal modelsSteatosisAKT Ser/ThrMiceMetabolic phenotyping
2013
Cellular 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 treatment
2011
Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease
Kumashiro N, Erion DM, Zhang D, Kahn M, Beddow SA, Chu X, Still CD, Gerhard GS, Han X, Dziura J, Petersen KF, Samuel VT, Shulman GI. Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 16381-16385. PMID: 21930939, PMCID: PMC3182681, DOI: 10.1073/pnas.1113359108.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseFatty liver diseaseHepatic DAG contentInsulin resistanceHepatic insulin resistanceLiver diseaseHepatic steatosisCellular mechanismsHomeostatic model assessmentInsulin resistance indexMarkers of inflammationType 2 diabetesER stress markersLipid dropletsHepatic diacylglycerol contentEndoplasmic reticulum stressActivation of PKCεLiver biopsyNondiabetic individualsHepatocellular lipidsInsulin sensitivityCytoplasmic lipid dropletsDAG contentResistance indexAnimal models