2009
Prevention of Hepatic Steatosis and Hepatic Insulin Resistance by Knockdown of cAMP Response Element-Binding Protein
Erion DM, Ignatova ID, Yonemitsu S, Nagai Y, Chatterjee P, Weismann D, Hsiao JJ, Zhang D, Iwasaki T, Stark R, Flannery C, Kahn M, Carmean CM, Yu XX, Murray SF, Bhanot S, Monia BP, Cline GW, Samuel VT, Shulman GI. Prevention of Hepatic Steatosis and Hepatic Insulin Resistance by Knockdown of cAMP Response Element-Binding Protein. Cell Metabolism 2009, 10: 499-506. PMID: 19945407, PMCID: PMC2799933, DOI: 10.1016/j.cmet.2009.10.007.Peer-Reviewed Original ResearchConceptsHepatic insulin resistanceNonalcoholic fatty liver diseaseCAMP response element-binding proteinInsulin resistanceResponse element-binding proteinASO treatmentElement-binding proteinCREB expressionType 2 diabetes mellitusOb/ob miceFatty liver diseaseHepatic triglyceride contentPlasma glucose concentrationFed rat modelAttractive therapeutic targetAntisense oligonucleotideDiabetes mellitusLiver diseaseZDF ratsHepatic steatosisOb micePostprandial hyperglycemiaPlasma cholesterolRat modelTriglyceride concentrations
2007
Overexpression of uncoupling protein 3 in skeletal muscle protects against fat-induced insulin resistance
Choi CS, Fillmore JJ, Kim JK, Liu ZX, Kim S, Collier EF, Kulkarni A, Distefano A, Hwang YJ, Kahn M, Chen Y, Yu C, Moore IK, Reznick RM, Higashimori T, Shulman GI. Overexpression of uncoupling protein 3 in skeletal muscle protects against fat-induced insulin resistance. Journal Of Clinical Investigation 2007, 117: 1995-2003. PMID: 17571165, PMCID: PMC1888566, DOI: 10.1172/jci13579.Peer-Reviewed Original ResearchMeSH KeywordsAgingAMP-Activated Protein KinasesAnimalsEnzyme ActivationGene Expression RegulationHormonesHumansInsulinInsulin ResistanceIon ChannelsIsoenzymesLipid MetabolismMaleMiceMice, TransgenicMitochondrial ProteinsMultienzyme ComplexesMuscle, SkeletalProtein Kinase CProtein Kinase C-thetaProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktUncoupling Protein 3Weight GainConceptsFat-induced insulin resistanceInsulin resistanceSkeletal muscleType 2 diabetes mellitusProtein 3IRS-2-associated PI3K activityHigh-fat dietType 2 diabetesHepatic insulin resistanceWild-type miceInsulin-stimulated glucose uptakeExcellent therapeutic targetInsulin-stimulated insulin receptor substrate 1Fatty acid metabolitesSerine kinase cascadeInsulin receptor substrate-1Intramyocellular fatDiabetes mellitusSkeletal muscle protectsReceptor substrate-1Therapeutic targetTransgenic miceAcid metabolitesPI3K activityGlucose uptakeInhibition 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