2022
Let-7 underlies metformin-induced inhibition of hepatic glucose production
Xie D, Chen F, Zhang Y, Shi B, Song J, Chaudhari K, Yang SH, Zhang GJ, Sun X, Taylor HS, Li D, Huang Y. Let-7 underlies metformin-induced inhibition of hepatic glucose production. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2122217119. PMID: 35344434, PMCID: PMC9169108, DOI: 10.1073/pnas.2122217119.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDisease Models, AnimalGlucoseHepatocytesHyperglycemiaHypoglycemic AgentsLiverMetforminMiceConceptsHepatic glucose productionAntidiabetic effectsMouse modelGlucose productionPotent antidiabetic actionsHepatocyte nuclear factor 4 alphaNuclear factor 4 alphaFunction mouse modelsHuman primary hepatocytesMetformin-induced inhibitionAntidiabetic actionTherapeutic effectGlucose homeostasisSuprapharmacological concentrationsRelevant dosesHepatic deliveryMetforminFetal isoformsPotential therapeuticsPrimary hepatocytesMost studiesLet-7Regulatory pathwaysHyperglycemiaDiabetes
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