Tranilast protects pancreatic beta-cells from palmitic acid-induced lipotoxicity via FoxO-1 inhibition
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Choi, Hye-Eun | - |
dc.contributor.author | Kim, Dong Young | - |
dc.contributor.author | Choi, Mi Jin | - |
dc.contributor.author | Kim, Jea Il | - |
dc.contributor.author | Kim, Ok-Hee | - |
dc.contributor.author | Lee, Jinwook | - |
dc.contributor.author | Seo, Eunhui | - |
dc.contributor.author | Cheon, Hyae Gyeong | - |
dc.date.accessioned | 2023-03-14T05:40:17Z | - |
dc.date.available | 2023-03-14T05:40:17Z | - |
dc.date.created | 2023-03-14 | - |
dc.date.issued | 2023-01 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/87062 | - |
dc.description.abstract | Tranilast, an anti-allergic drug used in the treatment of bronchial asthma, was identified as an inhibitor of the transcription factor Forkhead box O-1 (FoxO-1) by high throughput chemical library screening in the present study. Based on FoxO-1's role in apoptotic cell death and differentiation, we examined the effect of tranilast on palmitic acid (PA)-induced cell damage in INS-1 cells. Tranilast substantially inhibited lipoapoptosis and restored glucose-stimulated insulin secretion under high PA exposure. Moreover, PA-mediated downregulation of PDX-1, MafA, and insulin expression was attenuated by tranilast. PA-induced oxidative and ER stress were also reduced in the presence of tranilast. These protective effects were accompanied by increased phosphorylation and decreased nuclear translocation of FoxO-1. Conversely, the effects of tranilast were diminished when treated in transfected cells with FoxO-1 phosphorylation mutant (S256A), suggesting that the tranilast-mediated effects are associated with inactivation of FoxO-1. Examination of the in vivo effects of tranilast using wild type and diabetic db/db mice showed improved glucose tolerance along with FoxO-1 inactivation in the pancreas of the tranilast-treated groups. Thus, we report here that tranilast has protective effects against PA-induced lipotoxic stress in INS-1 cells, at least partly, via FoxO-1 inactivation, which results in improved glucose tolerance in vivo. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | NATURE PORTFOLIO | - |
dc.relation.isPartOf | SCIENTIFIC REPORTS | - |
dc.title | Tranilast protects pancreatic beta-cells from palmitic acid-induced lipotoxicity via FoxO-1 inhibition | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000913437400012 | - |
dc.identifier.doi | 10.1038/s41598-022-25428-3 | - |
dc.identifier.bibliographicCitation | SCIENTIFIC REPORTS, v.13, no.1 | - |
dc.description.isOpenAccess | Y | - |
dc.identifier.scopusid | 2-s2.0-85145428880 | - |
dc.citation.title | SCIENTIFIC REPORTS | - |
dc.citation.volume | 13 | - |
dc.citation.number | 1 | - |
dc.contributor.affiliatedAuthor | Choi, Hye-Eun | - |
dc.contributor.affiliatedAuthor | Kim, Dong Young | - |
dc.contributor.affiliatedAuthor | Choi, Mi Jin | - |
dc.contributor.affiliatedAuthor | Kim, Jea Il | - |
dc.contributor.affiliatedAuthor | Kim, Ok-Hee | - |
dc.contributor.affiliatedAuthor | Lee, Jinwook | - |
dc.contributor.affiliatedAuthor | Seo, Eunhui | - |
dc.contributor.affiliatedAuthor | Cheon, Hyae Gyeong | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | ENDOPLASMIC-RETICULUM STRESS | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | FATTY-ACID | - |
dc.subject.keywordPlus | INSULIN | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordPlus | DIFFERENTIATION | - |
dc.subject.keywordPlus | CERAMIDE | - |
dc.subject.keywordPlus | PROTEINS | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
1342, Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, Republic of Korea(13120)031-750-5114
COPYRIGHT 2020 Gachon University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.