An MG53-IRS1-interaction disruptor ameliorates insulin resistance
DC Field | Value | Language |
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dc.contributor.author | Park, Jun Sub | - |
dc.contributor.author | Lee, Hyun | - |
dc.contributor.author | Choi, Bo Woon | - |
dc.contributor.author | Ro, Seonggu | - |
dc.contributor.author | Lee, Doyoung | - |
dc.contributor.author | Na, Jeong Eun | - |
dc.contributor.author | Hong, Jeoung-Ho | - |
dc.contributor.author | Lee, Jae-Seon | - |
dc.contributor.author | Kim, Bong-Woo | - |
dc.contributor.author | Ko, Young-Gyu | - |
dc.date.accessioned | 2021-09-02T10:20:36Z | - |
dc.date.available | 2021-09-02T10:20:36Z | - |
dc.date.created | 2021-06-16 | - |
dc.date.issued | 2018-06-06 | - |
dc.identifier.issn | 1226-3613 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/74959 | - |
dc.description.abstract | Mitsugumin 53 (MG53) is an E3 ligase that induces insulin receptor substrate-1 (IRS-1) ubiquitination and degradation in skeletal muscle. We previously demonstrated that the pharmaceutical disruption of the MG53-IRS-1 interaction improves insulin sensitivity by abrogating IRS-1 ubiquitination and increasing IRS-1 levels in C2C12 myotubes. Here, we developed a novel MG53-IRS-1 interaction disruptor (MID-00935) that ameliorates insulin resistance in diet-induced obese (DIO) mice. MID-00935 disrupted the molecular interaction of MG53 and IRS-1, abrogated MG53-induced IRS-1 ubiquitination and degradation and improved insulin signaling in C2C12 myotubes. Oral administration of MID-00935 increased insulin-induced IRS-1, Akt, and Erk phosphorylation via increasing IRS-1 levels in the skeletal muscle of DIO mice. In DIO mice, MID-00935 treatment lowered fasting blood glucose levels and improved glucose disposal in glucose and insulin tolerance tests. These results suggest that MID-00935 may be a potential muscle-targeting drug candidate for treating insulin resistance. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | TYPE-2 DIABETES-MELLITUS | - |
dc.subject | HUMAN MG53 PROTEIN | - |
dc.subject | RECEPTOR SUBSTRATE-1 | - |
dc.subject | PHOSPHATIDYLINOSITOL 3-KINASE | - |
dc.subject | MEMBRANE REPAIR | - |
dc.subject | SKELETAL-MUSCLE | - |
dc.subject | MUSCULAR-DYSTROPHY | - |
dc.subject | REPERFUSION INJURY | - |
dc.subject | METFORMIN | - |
dc.subject | MICE | - |
dc.title | An MG53-IRS1-interaction disruptor ameliorates insulin resistance | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Hyun | - |
dc.contributor.affiliatedAuthor | Hong, Jeoung-Ho | - |
dc.contributor.affiliatedAuthor | Kim, Bong-Woo | - |
dc.contributor.affiliatedAuthor | Ko, Young-Gyu | - |
dc.identifier.doi | 10.1038/s12276-018-0099-9 | - |
dc.identifier.scopusid | 2-s2.0-85048276218 | - |
dc.identifier.wosid | 000434699300001 | - |
dc.identifier.bibliographicCitation | EXPERIMENTAL AND MOLECULAR MEDICINE, v.50 | - |
dc.relation.isPartOf | EXPERIMENTAL AND MOLECULAR MEDICINE | - |
dc.citation.title | EXPERIMENTAL AND MOLECULAR MEDICINE | - |
dc.citation.volume | 50 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.identifier.kciid | ART002356411 | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.description.journalRegisteredClass | kci | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.subject.keywordPlus | TYPE-2 DIABETES-MELLITUS | - |
dc.subject.keywordPlus | HUMAN MG53 PROTEIN | - |
dc.subject.keywordPlus | RECEPTOR SUBSTRATE-1 | - |
dc.subject.keywordPlus | PHOSPHATIDYLINOSITOL 3-KINASE | - |
dc.subject.keywordPlus | MEMBRANE REPAIR | - |
dc.subject.keywordPlus | SKELETAL-MUSCLE | - |
dc.subject.keywordPlus | MUSCULAR-DYSTROPHY | - |
dc.subject.keywordPlus | REPERFUSION INJURY | - |
dc.subject.keywordPlus | METFORMIN | - |
dc.subject.keywordPlus | MICE | - |
dc.subject.keywordAuthor | drug discovery | - |
dc.subject.keywordAuthor | Type 2 diabetes | - |
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