2010
Deletion of the α-Arrestin Protein Txnip in Mice Promotes Adiposity and Adipogenesis While Preserving Insulin Sensitivity
Chutkow WA, Birkenfeld AL, Brown JD, Lee HY, Frederick DW, Yoshioka J, Patwari P, Kursawe R, Cushman SW, Plutzky J, Shulman GI, Samuel VT, Lee RT. Deletion of the α-Arrestin Protein Txnip in Mice Promotes Adiposity and Adipogenesis While Preserving Insulin Sensitivity. Diabetes 2010, 59: 1424-1434. PMID: 20299477, PMCID: PMC2874703, DOI: 10.2337/db09-1212.Peer-Reviewed Original ResearchConceptsTxnip knockout miceInsulin resistanceInsulin sensitivityKnockout miceInsulin responsivenessTXNIP expressionSkeletal muscleWild-type littermate control miceStandard chow dietType 2 diabetes pathogenesisHigh-fat dietHigh-fat feedingLittermate control miceGene-deleted miceInhibits glucose uptakeControl miceChow dietAdipose massMore insulinCaloric excessFat massDiabetes pathogenesisMouse embryonic fibroblastsRegulator of adipogenesisPPARgamma expression
2009
Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with Type 2 Diabetes
Samuel VT, Beddow SA, Iwasaki T, Zhang XM, Chu X, Still CD, Gerhard GS, Shulman GI. Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with Type 2 Diabetes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 12121-12126. PMID: 19587243, PMCID: PMC2707270, DOI: 10.1073/pnas.0812547106.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsDiabetes Mellitus, Type 2Dietary FatsFastingFeeding BehaviorFemaleGene Expression Regulation, EnzymologicGluconeogenesisGlucose-6-PhosphataseHumansHyperglycemiaHyperinsulinismInsulin Infusion SystemsLiverMaleMiddle AgedPhosphoenolpyruvate Carboxykinase (ATP)RatsRats, Sprague-DawleyStreptozocinConceptsHigh-fat feedingEndogenous glucose productionHFF ratsExpression of PEPCKHepatic expressionType 2 diabetes mellitusBeta-cell compensationBeta-cell responseFirst rat modelPortal vein infusionLiver biopsy samplesHigher plasma glucosePhosphoenolpyruvate carboxykinaseBariatric surgeryT2DM patientsDiabetes mellitusInsulin resistancePlasma insulinPlasma glucosePortal infusionRat modelRodent modelsVein infusionHyperglycemiaKey gluconeogenic enzymes
2007
Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease
Samuel VT, Liu ZX, Wang A, Beddow SA, Geisler JG, Kahn M, Zhang XM, Monia BP, Bhanot S, Shulman GI. Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease. Journal Of Clinical Investigation 2007, 117: 739-745. PMID: 17318260, PMCID: PMC1797607, DOI: 10.1172/jci30400.Peer-Reviewed Original ResearchConceptsHepatic insulin resistanceNonalcoholic fatty liver diseaseFatty liver diseaseInsulin resistanceHigh-fat feedingLiver diseaseFat-induced hepatic insulin resistanceType 2 diabetes mellitusType 2 diabetesHepatic fat accumulationNovel therapeutic targetInsulin receptor kinase activityDiabetes mellitusHepatic steatosisFat accumulationRats resultsTherapeutic targetHepatic insulinReceptor kinase activityProtein kinase CεInsulin receptorCausal roleIsoforms of PKCAntisense oligonucleotideRats
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