Capmatinib improves insulin sensitivity and inflammation in palmitate-treated C2C12 myocytes through the PPARδ/p38-dependent pathway
Özet
© 2021 Elsevier B.V.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.
Anahtar kelimeler
Sürdürülebilir Kalkınma Amaçları
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SKA 3: Sağlıklı Bireyler
Atıf için künye
Jung, T. W., Lee, H. J., Pyun, D. H., Kim, T. J., Bang, J. S., Song, J., Shin, Y. K., Hassıbelnaby, A. M. A., & Jeong, J. H. (2021). Capmatinib improves insulin sensitivity and inflammation in palmitate-treated C2C12 myocytes through the PPARδ/p38-dependent pathway. MOLECULAR AND CELLULAR ENDOCRINOLOGY, 534. https://doi.org/10.1016/j.mce.2021.111364
BibTeX
@article{jung2021-209744,
author = {Jung, Tae Woo and Lee, Hyun Jung and Pyun, Do Hyeon and Kim, Tae Jin and Bang, Joon Seok and Song, Jin-Ho and Shin, Yong Kyoo and Hassıbelnaby, Abdelaty Mostafa Abdelaty and Jeong, Ji Hoon},
title = {Capmatinib improves insulin sensitivity and inflammation in palmitate-treated C2C12 myocytes through the PPARδ/p38-dependent pathway},
journal = {MOLECULAR AND CELLULAR ENDOCRINOLOGY},
year = {2021},
volume = {534},
issn = {0303-7207},
doi = {10.1016/j.mce.2021.111364},
url = {https://akademik.atauni.edu.tr/yayinlar/209744-capmatinib-improves-insulin-sensitivity-and-inflammation-in-palmitate-treated}
}