Capmatinib improves insulin sensitivity and inflammation in palmitate-treated C2C12 myocytes through the PPARδ/p38-dependent pathway

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 NF kappa B and I kappa B, in palmitate-treated C2C12 myocytes. Further, it augmented PPAR delta expression and suppressed palmitate-induced p38 phosphorylation in a dose-dependent manner. siRNA-mediated suppression of PPAR delta 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 PPAR delta/p38 signaling-mediated suppression of inflammation. These results may represent a novel therapeutic approach that could halt insulin resistance and type 2 diabetes.

Journal

MOLECULAR AND CELLULAR ENDOCRINOLOGY

Year

2021

Volume

534

ISSN

0303-7207

eISSN

1872-8057

DOI

10.1016/j.mce.2021.111364

WoS UID

WOS:000681260500006