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An autophagy enhancer ameliorates diabetes of human IAPP-transgenic mice through clearance of amyloidogenic oligomer

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dc.contributor.author김진영-
dc.contributor.author이명식-
dc.date.accessioned2021-09-29T01:15:31Z-
dc.date.available2021-09-29T01:15:31Z-
dc.date.issued2021-01-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/184272-
dc.description.abstractWe have reported that autophagy is crucial for clearance of amyloidogenic human IAPP (hIAPP) oligomer, suggesting that an autophagy enhancer could be a therapeutic modality against human diabetes with amyloid accumulation. Here, we show that a recently identified autophagy enhancer (MSL-7) reduces hIAPP oligomer accumulation in human induced pluripotent stem cell-derived β-cells (hiPSC-β-cells) and diminishes oligomer-mediated apoptosis of β-cells. Protective effects of MSL-7 against hIAPP oligomer accumulation and hIAPP oligomer-mediated β-cell death are significantly reduced in cells with knockout of MiTF/TFE family members such as Tfeb or Tfe3. MSL-7 improves glucose tolerance and β-cell function of hIAPP+ mice on high-fat diet, accompanied by reduced hIAPP oligomer/amyloid accumulation and β-cell apoptosis. Protective effects of MSL-7 against hIAPP oligomer-mediated β-cell death and the development of diabetes are also significantly reduced by β-cell-specific knockout of Tfeb. These results suggest that an autophagy enhancer could have therapeutic potential against human diabetes characterized by islet amyloid accumulation.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherNature Pub. Group-
dc.relation.isPartOfNATURE COMMUNICATIONS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAmyloid / metabolism*-
dc.subject.MESHAmyloidogenic Proteins / metabolism*-
dc.subject.MESHAnimals-
dc.subject.MESHApoptosis / physiology-
dc.subject.MESHAutophagy / physiology*-
dc.subject.MESHBasic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics-
dc.subject.MESHDiabetes Mellitus, Type 2 / metabolism*-
dc.subject.MESHGene Knockout Techniques-
dc.subject.MESHHumans-
dc.subject.MESHInduced Pluripotent Stem Cells / metabolism-
dc.subject.MESHInsulin-Secreting Cells-
dc.subject.MESHIslet Amyloid Polypeptide / genetics*-
dc.subject.MESHIslet Amyloid Polypeptide / metabolism*-
dc.subject.MESHMacroautophagy / physiology-
dc.subject.MESHMice-
dc.subject.MESHMice, Transgenic-
dc.titleAn autophagy enhancer ameliorates diabetes of human IAPP-transgenic mice through clearance of amyloidogenic oligomer-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentBioMedical Science Institute (의생명과학부)-
dc.contributor.googleauthorJinyoung Kim-
dc.contributor.googleauthorKihyoun Park-
dc.contributor.googleauthorMin Jung Kim-
dc.contributor.googleauthorHyejin Lim-
dc.contributor.googleauthorKook Hwan Kim-
dc.contributor.googleauthorSun-Woo Kim-
dc.contributor.googleauthorEun-Seo Lee-
dc.contributor.googleauthorHyongbum Henry Kim-
dc.contributor.googleauthorSung Joo Kim-
dc.contributor.googleauthorKyu Yeon Hur-
dc.contributor.googleauthorJae Hyeon Kim-
dc.contributor.googleauthorJin Hee Ahn-
dc.contributor.googleauthorKun-Ho Yoon-
dc.contributor.googleauthorJi-Won Kim-
dc.contributor.googleauthorMyung-Shik Lee-
dc.identifier.doi10.1038/s41467-020-20454-z-
dc.contributor.localIdA05786-
dc.contributor.localIdA02752-
dc.relation.journalcodeJ02293-
dc.identifier.eissn2041-1723-
dc.identifier.pmid33420039-
dc.contributor.alternativeNameKim, Jinyoung-
dc.contributor.affiliatedAuthor김진영-
dc.contributor.affiliatedAuthor이명식-
dc.citation.volume12-
dc.citation.number1-
dc.citation.startPage183-
dc.identifier.bibliographicCitationNATURE COMMUNICATIONS, Vol.12(1) : 183, 2021-01-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers

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