2024
Skeletal muscle TET3 promotes insulin resistance through destabilisation of PGC-1α
Liu B, Xie D, Huang X, Jin S, Dai Y, Sun X, Li D, Bennett A, Diano S, Huang Y. Skeletal muscle TET3 promotes insulin resistance through destabilisation of PGC-1α. Diabetologia 2024, 67: 724-737. PMID: 38216792, PMCID: PMC10904493, DOI: 10.1007/s00125-023-06073-5.Peer-Reviewed Original ResearchConceptsTen-eleven translocationMuscle insulin sensitivityRNA-seqPGC-1aRegulation of muscle insulin sensitivityType 2 diabetesAnalysis of RNA-seqResponse to environmental cuesGenome-wide expression profilingWild-typeHFD-fedHFD-induced insulin resistanceHigh-fat diet (HFD)-inducedExpression levelsMaintenance of glucoseSkeletal muscle insulin sensitivityAccession numbersSkeletal muscleEnhanced glucose toleranceFamily dioxygenasesMitochondrial respirationSkeletal muscle of humansEnvironmental cuesMitochondrial functionBiological processes
2020
Hepatic TET3 contributes to type-2 diabetes by inducing the HNF4α fetal isoform
Da Li, Cao T, Sun X, Jin S, Di Xie, Huang X, Yang X, Carmichael GG, Taylor HS, Diano S, Huang Y. Hepatic TET3 contributes to type-2 diabetes by inducing the HNF4α fetal isoform. Nature Communications 2020, 11: 342. PMID: 31953394, PMCID: PMC6969024, DOI: 10.1038/s41467-019-14185-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDiabetes Mellitus, Type 2DioxygenasesDisease Models, AnimalDNA DemethylationDNA MethylationDNA-Binding ProteinsFastingGene Expression RegulationGlucagonGlucoseHepatocyte Nuclear Factor 3-betaHepatocyte Nuclear Factor 4LiverMaleMiceMice, Inbred C57BLMice, KnockoutPromoter Regions, GeneticProtein IsoformsTranscriptional ActivationTranscriptomeUp-RegulationConceptsHepatic glucose productionType 2 diabetesGlucose homeostasisAdult liverSystemic glucose homeostasisPotential therapeutic targetGenetic mouse modelsFetal versionKey gluconeogenic genesMouse modelTherapeutic targetHNF4α functionGlucose productionFetal isoformsLiverT2D.DiabetesPromoter demethylationGluconeogenic genesTET3 overexpressionHNF4αHomeostasisTET3Regulatory mechanismsIsoforms
2018
Elevated hepatic expression of H19 long noncoding RNA contributes to diabetic hyperglycemia
Zhang N, Geng T, Wang Z, Zhang R, Cao T, Camporez JP, Cai SY, Liu Y, Dandolo L, Shulman GI, Carmichael GG, Taylor HS, Huang Y. Elevated hepatic expression of H19 long noncoding RNA contributes to diabetic hyperglycemia. JCI Insight 2018, 3: e120304. PMID: 29769440, PMCID: PMC6012507, DOI: 10.1172/jci.insight.120304.Peer-Reviewed Original ResearchConceptsHepatic glucose productionGenome-wide methylationExpression of Hnf4aGluconeogenic transcription factorsDiabetic hyperglycemiaH19 depletionTranscriptome analysisTranscription factorsExpression of H19Molecular mechanismsDiet-induced diabetic miceExcessive hepatic glucose productionType 2 diabetesInsulin-dependent suppressionElevated hepatic expressionH19 knockdownH19Promoter methylationMechanistic explanationMethylationDiabetic patientsRNADiabetic miceInsulin resistanceH19 overexpression