An MG53-IRS1-interaction disruptor ameliorates insulin resistance
- Authors
- Park, Jun Sub; Lee, Hyun; Choi, Bo Woon; Ro, Seonggu; Lee, Doyoung; Na, Jeong Eun; Hong, Jeoung-Ho; Lee, Jae-Seon; Kim, Bong-Woo; Ko, Young-Gyu
- Issue Date
- 6-6월-2018
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- drug discovery; Type 2 diabetes
- Citation
- EXPERIMENTAL AND MOLECULAR MEDICINE, v.50
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- EXPERIMENTAL AND MOLECULAR MEDICINE
- Volume
- 50
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/74959
- DOI
- 10.1038/s12276-018-0099-9
- ISSN
- 1226-3613
- 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.
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Collections - Graduate School > Department of Life Sciences > 1. Journal Articles
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