Capmatinib improves insulin sensitivity and inflammation in palmitate-treated C2C12 myocytes through the PPARδ/p38-dependent pathway
- Authors
- Jung, Tae Woo; Lee, Hyun Jung; Pyun, Do Hyeon; Kim, Tae Jin; Bang, Joon Seok; Song, Jin-Ho; Shin, Yong Kyoo; Abd El-Aty A.M.; Jeong, Ji Hoon
- Issue Date
- Aug-2021
- Publisher
- Elsevier Ireland Ltd
- Keywords
- Capmatinib; Inflammation; Insulin resistance; Myocyte; p38; PPARδ
- Citation
- Molecular and Cellular Endocrinology, v.534, pp 1 - 7
- Pages
- 7
- Journal Title
- Molecular and Cellular Endocrinology
- Volume
- 534
- Start Page
- 1
- End Page
- 7
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/146435
- DOI
- 10.1016/j.mce.2021.111364
- ISSN
- 0303-7207
1872-8057
- Abstract
- Capmatinib (CAP) has been used to treat metastatic non-small lung cancer (NSCL) and suppress inflammation. It causes hypoglycemia in NSCL patients. Therefore, it is expected that CAP improves inflammation-mediated insulin resistance due to its anti-inflammatory effect. However, the impacts of CAP on insulin signaling in skeletal muscle cells have not yet been fully elucidated. Herein, we investigated the effect of CAP on insulin resistance in palmitate-treated C2C12 myocytes and explored the related molecular mechanisms. We found that treatment of C2C12 myocytes with CAP reversed palmitate-induced impairment of insulin signaling and glucose uptake. CAP treatment ameliorated phosphorylation of inflammatory markers, including NFκB and IκB, in palmitate-treated C2C12 myocytes. Further, it augmented PPARδ expression and suppressed palmitate-induced p38 phosphorylation in a dose-dependent manner. siRNA-mediated suppression of PPARδ abolished the effects of CAP on palmitate-induced insulin resistance and inflammation as well as p38 phosphorylation. Therefore, it has been shown that CAP treatment ameliorates insulin resistance in palmitate-treated C2C12 myocytes via PPARδ/p38 signaling-mediated suppression of inflammation. These results may represent a novel therapeutic approach that could halt insulin resistance and type 2 diabetes. © 2021 Elsevier B.V.
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