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

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:534

Article

Jung, Tae Woo¹  Lee, Hyun Jung^2,3  Pyun, Do Hyeon¹  Kim, Tae Jin¹  Bang, Joon Seok⁴  Song, Jin-Ho¹  Shin, Yong Kyoo¹  Abd El-Aty, A. M.^5,6,7  Jeong, Ji Hoon^1,3 

[1] Chung Ang Univ, Coll Med, Dept Pharmacol, Seoul, South Korea

[2] Chung Ang Univ, Coll Med, Dept Anat & Cell Biol, Seoul, South Korea

[3] Chung Ang Univ, Dept Global Innovat Drugs, Grad Sch, Seoul, South Korea

[4] Sookmyung Womens Univ, Coll Pharm, Seoul, South Korea

[5] Qilu Univ Technol, Shandong Acad Sci, Coll Food Sci & Engn, State Key Lab Biobased Mat & Green Papermaking, Jinan 250353, Peoples R China

[6] Cairo Univ, Fac Vet Med, Dept Pharmacol, Giza 12211, Egypt

[7] Ataturk Univ, Med Fac, Dept Med Pharmacol, Erzurum, Turkey

关键词: Capmatinib;    PPAR delta;    p38;    Myocyte;    Inflammation;    Insulin resistance;   

DOI  :  10.1016/j.mce.2021.111364

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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