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Txnip contributes to impaired glucose tolerance by upregulating the expression of genes involved in hepatic gluconeogenesis in mice

DC FieldValueLanguage
dc.contributor.author김미영-
dc.contributor.author김태현-
dc.contributor.author박주만-
dc.contributor.author안용호-
dc.contributor.author조성호-
dc.date.accessioned2014-12-18T09:35:15Z-
dc.date.available2014-12-18T09:35:15Z-
dc.date.issued2013-
dc.identifier.issn0012-186X-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/88450-
dc.description.abstractAIMS/HYPOTHESIS: Thioredoxin-interacting protein (TXNIP) is upregulated in the hyperglycaemic state and represses glucose uptake, resulting in imbalanced glucose homeostasis. In this study, we propose a mechanism of how TXNIP impairs hepatic glucose tolerance at the transcriptional level. METHODS: We administered adenoviral Txnip (Ad-Txnip) to normal mice and performed intraperitoneal glucose tolerance tests (IPGTT), insulin tolerance tests (ITT) and pyruvate tolerance tests (PTT). After Ad-Txnip administration, the expression of genes involved in glucose metabolism, including G6pc and Gck, was analysed using quantitative real-time PCR and western blot. To understand the increased G6pc expression in liver resulting from Txnip overexpression, we performed pull-down assays for TXNIP and small heterodimer partner (SHP). Luciferase reporter assays and chromatin immunoprecipitation using the Txnip promoter were performed to elucidate the interrelationship between carbohydrate response element-binding protein (ChREBP) and transcription factor E3 (TFE3) in the regulation of Txnip expression. RESULTS: Overabundance of TXNIP resulted in impaired glucose, insulin and pyruvate tolerance in normal mice. Ad-Txnip transduction upregulated G6pc expression and caused a decrease in Gck levels in the liver of normal mice and primary hepatocytes. TXNIP increased G6pc expression by forming a complex with SHP, which is known to be a negative modulator of gluconeogenesis. Txnip expression in mouse models of diabetes was decreased by Ad-Tfe3 administration, suggesting that TFE3 may play a negative role through competition with ChREBP at the E-box of the Txnip promoter. CONCLUSIONS/INTERPRETATION: We demonstrated that TXNIP impairs glucose and insulin tolerance in mice by upregulating G6pc through interaction with SHP.-
dc.description.statementOfResponsibilityopen-
dc.relation.isPartOfDIABETOLOGIA-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHBasic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism-
dc.subject.MESHBlotting, Western-
dc.subject.MESHCarrier Proteins/genetics-
dc.subject.MESHCarrier Proteins/metabolism*-
dc.subject.MESHChromatin Immunoprecipitation-
dc.subject.MESHDiabetes Mellitus, Experimental/metabolism*-
dc.subject.MESHGluconeogenesis*-
dc.subject.MESHGlucose Intolerance/metabolism*-
dc.subject.MESHGlucose Tolerance Test-
dc.subject.MESHGlucose-6-Phosphatase/genetics-
dc.subject.MESHGlucose-6-Phosphatase/metabolism*-
dc.subject.MESHLiver/metabolism*-
dc.subject.MESHMale-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred C57BL-
dc.subject.MESHMice, Inbred NOD-
dc.subject.MESHNuclear Proteins/metabolism-
dc.subject.MESHPromoter Regions, Genetic-
dc.subject.MESHReal-Time Polymerase Chain Reaction-
dc.subject.MESHThioredoxins/genetics-
dc.subject.MESHThioredoxins/metabolism*-
dc.subject.MESHTranscription Factors/metabolism-
dc.subject.MESHTranscriptional Activation-
dc.subject.MESHUp-Regulation-
dc.titleTxnip contributes to impaired glucose tolerance by upregulating the expression of genes involved in hepatic gluconeogenesis in mice-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Biochemistry & Molecular Biology (생화학,분자생물학)-
dc.contributor.googleauthorSeong Ho Jo-
dc.contributor.googleauthorMi Young Kim-
dc.contributor.googleauthorJoo Man Park-
dc.contributor.googleauthorTae Hyun Kim-
dc.contributor.googleauthorYong Ho Ahn-
dc.identifier.doi10.1007/s00125-013-3050-6-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00446-
dc.contributor.localIdA01666-
dc.contributor.localIdA02249-
dc.contributor.localIdA03838-
dc.contributor.localIdA01081-
dc.relation.journalcodeJ00727-
dc.identifier.eissn1432-0428-
dc.identifier.pmid24037087-
dc.identifier.urlhttp://link.springer.com/article/10.1007%2Fs00125-013-3050-6-
dc.subject.keywordAnimals-
dc.subject.keywordBasic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism-
dc.subject.keywordBlotting, Western-
dc.subject.keywordCarrier Proteins/genetics-
dc.subject.keywordCarrier Proteins/metabolism*-
dc.subject.keywordChromatin Immunoprecipitation-
dc.subject.keywordDiabetes Mellitus, Experimental/metabolism*-
dc.subject.keywordGluconeogenesis*-
dc.subject.keywordGlucose Intolerance/metabolism*-
dc.subject.keywordGlucose Tolerance Test-
dc.subject.keywordGlucose-6-Phosphatase/genetics-
dc.subject.keywordGlucose-6-Phosphatase/metabolism*-
dc.subject.keywordLiver/metabolism*-
dc.subject.keywordMale-
dc.subject.keywordMice-
dc.subject.keywordMice, Inbred C57BL-
dc.subject.keywordMice, Inbred NOD-
dc.subject.keywordNuclear Proteins/metabolism-
dc.subject.keywordPromoter Regions, Genetic-
dc.subject.keywordReal-Time Polymerase Chain Reaction-
dc.subject.keywordThioredoxins/genetics-
dc.subject.keywordThioredoxins/metabolism*-
dc.subject.keywordTranscription Factors/metabolism-
dc.subject.keywordTranscriptional Activation-
dc.subject.keywordUp-Regulation-
dc.contributor.alternativeNameKim, Mi Young-
dc.contributor.alternativeNameKim, Tae Hyun-
dc.contributor.alternativeNamePark, Joo Man-
dc.contributor.alternativeNameAhn, Yong Ho-
dc.contributor.alternativeNameJo, Seong Ho-
dc.contributor.affiliatedAuthorKim, Mi Young-
dc.contributor.affiliatedAuthorPark, Joo Man-
dc.contributor.affiliatedAuthorAhn, Yong Ho-
dc.contributor.affiliatedAuthorJo, Seong Ho-
dc.contributor.affiliatedAuthorKim, Tae Hyun-
dc.rights.accessRightsnot free-
dc.citation.volume56-
dc.citation.number12-
dc.citation.startPage2723-
dc.citation.endPage2732-
dc.identifier.bibliographicCitationDIABETOLOGIA, Vol.56(12) : 2723-2732, 2013-
dc.identifier.rimsid34042-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers

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