2013
Thyroid hormone receptor-β agonists prevent hepatic steatosis in fat-fed rats but impair insulin sensitivity via discrete pathways
Vatner DF, Weismann D, Beddow SA, Kumashiro N, Erion DM, Liao XH, Grover GJ, Webb P, Phillips KJ, Weiss RE, Bogan JS, Baxter J, Shulman GI, Samuel VT. Thyroid hormone receptor-β agonists prevent hepatic steatosis in fat-fed rats but impair insulin sensitivity via discrete pathways. AJP Endocrinology And Metabolism 2013, 305: e89-e100. PMID: 23651850, PMCID: PMC3725564, DOI: 10.1152/ajpendo.00573.2012.Peer-Reviewed Original ResearchMeSH KeywordsAcetatesAnilidesAnimalsDietary FatsFatty LiverGene ExpressionGluconeogenesisGlucose Transporter Type 4HyperglycemiaHyperinsulinismInsulin ResistanceMaleMuscle, SkeletalNon-alcoholic Fatty Liver DiseasePhenolsRatsRats, Sprague-DawleySignal TransductionThyroid Hormone Receptors betaTriglyceridesConceptsEndogenous glucose productionHepatic insulin sensitivityInsulin sensitivityHepatic steatosisFat-fed ratsInsulin-stimulated peripheral glucose disposalTRβ agonistsInsulin-stimulated skeletal muscle glucose uptakePotent lipid-lowering drugsNonalcoholic fatty liver diseaseWhite adipose tissue lipolysisMale Sprague-Dawley ratsSkeletal muscle glucose uptakeGC-1 treatmentPeripheral glucose disposalFatty liver diseaseImpairs insulin sensitivityLipid-lowering drugsHepatic triglyceride contentAdipose tissue lipolysisMuscle glucose uptakeSprague-Dawley ratsHepatic insulin resistanceSkeletal muscle insulinPotential adverse effects
2004
Mechanism of Hepatic Insulin Resistance in Non-alcoholic Fatty Liver Disease*
Samuel VT, Liu ZX, Qu X, Elder BD, Bilz S, Befroy D, Romanelli AJ, Shulman GI. Mechanism of Hepatic Insulin Resistance in Non-alcoholic Fatty Liver Disease*. Journal Of Biological Chemistry 2004, 279: 32345-32353. PMID: 15166226, DOI: 10.1074/jbc.m313478200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCell MembraneCytosolDeoxyglucoseEnzyme ActivationFatty AcidsFatty LiverGlycogenGlycogen SynthaseInsulinInsulin ResistanceLipid MetabolismLiverMaleMitogen-Activated Protein Kinase 8Mitogen-Activated Protein KinasesPhosphorylationPrecipitin TestsProtein IsoformsProtein Kinase CProtein Kinase C-epsilonProtein TransportRatsRats, Sprague-DawleyRNA, MessengerSignal TransductionTime FactorsTyrosineConceptsHepatic insulin resistanceNon-alcoholic fatty liver diseaseEndogenous glucose productionFatty liver diseaseInsulin resistanceHepatic fat accumulationFat feedingLiver diseaseFat accumulationFF groupInsulin-stimulated peripheral glucose disposalShort-term fat feedingSkeletal muscle fat contentBasal endogenous glucose productionShort-term high-fat feedingPeripheral glucose disposalHigh-fat feedingIRS-1PKC-epsilonAbility of insulinAcyl-CoA contentInsulin-stimulated IRS-1IRS-2 tyrosine phosphorylationLiver triglyceridesFatty liver
2003
Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning
Weiss R, Dufour S, Taksali SE, Tamborlane WV, Petersen KF, Bonadonna RC, Boselli L, Barbetta G, Allen K, Rife F, Savoye M, Dziura J, Sherwin R, Shulman GI, Caprio S. Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning. The Lancet 2003, 362: 951-957. PMID: 14511928, PMCID: PMC2995523, DOI: 10.1016/s0140-6736(03)14364-4.Peer-Reviewed Original ResearchConceptsImpaired glucose toleranceNormal glucose toleranceGlucose toleranceObese childrenInsulin resistanceObese adolescentsGlucose disposalInsulin sensitivitySevere peripheral insulin resistanceNon-oxidative glucose metabolismSubcutaneous fatH plasma glucose concentrationsAbdominal fat partitioningVisceral lipid contentsPeripheral glucose disposalHigher intramyocellular lipid contentAbdominal fat distributionDegree of obesityIntramyocellular lipid contentPeripheral insulin resistanceHigh visceral fatAbdominal subcutaneous fatEuglycaemic hyperinsulinaemic clampSevere insulin resistancePlasma glucose concentration
1998
Efficacy and Metabolic Effects of Metformin and Troglitazone in Type II Diabetes Mellitus
Inzucchi S, Maggs D, Spollett G, Page S, Rife F, Walton V, Shulman G. Efficacy and Metabolic Effects of Metformin and Troglitazone in Type II Diabetes Mellitus. New England Journal Of Medicine 1998, 338: 867-873. PMID: 9516221, DOI: 10.1056/nejm199803263381303.Peer-Reviewed Original ResearchConceptsEndogenous glucose productionPlasma glucose concentrationPostprandial plasma glucose concentrationsPeripheral glucose disposalType 2 diabetesMetformin therapyTroglitazone therapyGlucose disposalGlucose productionHemoglobin valuesGlucose concentrationType II diabetes mellitusAdditive beneficial effectsSingle-drug therapyDiabetes mellitusGlycemic controlCombination therapyPoor responseMetabolic effectsPhysiologic effectsMetforminPatientsTherapyTroglitazoneBeneficial effects
1991
The effect of CP 68,722, a thiozolidinedione derivative, on insulin sensitivity in lean and obese Zucker rats
Bowen L, Stein P, Stevenson R, Shulman G. The effect of CP 68,722, a thiozolidinedione derivative, on insulin sensitivity in lean and obese Zucker rats. Metabolism 1991, 40: 1025-1030. PMID: 1943727, DOI: 10.1016/0026-0495(91)90124-f.Peer-Reviewed Original ResearchConceptsHepatic glucose productionInsulin-induced suppressionObese animalsObese Zucker ratsGlucose disposalInsulin sensitivityDrug treatmentFree fatty acidsZucker ratsHigher insulin infusion ratesEuglycemic hyperinsulinemic clamp techniqueInsulin-resistant animal modelsPeripheral glucose disposalHyperinsulinemic clamp techniquePeripheral glucose uptakeInsulin infusion rateInsulin clampInsulin suppressionKetone levelsInfusion rateAnimal modelsClamp techniqueEffect of CPLean animalsLipid metabolism
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