Palmitate induced insulin resistance by PKCtheta-dependent activation of mTOR/S6K pathway in C2C12 myotubes.
Palmitate induced insulin resistance by PKCtheta-dependent activation of mTOR/S6K pathway in C2C12 myotubes.
复制标题
棕榈酸通过 C2C12 肌管中 mTOR/S6K 通路的 PKCtheta 依赖性激活诱导胰岛素抵抗。
DOI：
10.1055/s-0030-1252069
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发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Changhua Wang
中科院分区：
文献类型：
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作者：
Xiong Wang;Wanqui Yu;Ahmed Nawaz;Feng Guan;Shengrong Sun;Changhua Wang
棕榈酸诱导的骨骼肌细胞胰岛素抵抗的潜在机制尚不清楚。在这项研究中，我们发现棕榈酸酯抑制C2 C12肌管中的胰岛素信号，伴随着蛋白激酶C-θ（PKCΘ）磷酸化的增强。棕榈酸酯对胰岛素信号传导的抑制作用在PKCΘ-和mTOR（雷帕霉素的哺乳动物靶标）缺陷的C2 C12肌管和用雷帕霉素预处理的C2 C12肌管中减弱。此外，棕榈酸增强的mTOR和p70核糖体S6激酶（S6 K）的磷酸化在PKC θ缺陷的C2 C12肌管和用PKC θ假底物处理的C2 C12肌管中减弱。综上所述，我们的结果表明棕榈酸诱导的C2 C12肌管胰岛素抵抗是由PKCΘ/mTOR/S6 K通路介导的。
The underlying mechanism of palmitate-induced insulin resistance in skeletal muscle cells is obscure. In this study, we showed that palmitate inhibited the insulin signaling in C2C12 myotubes, accompanied with the enhanced phosphorylation of protein kinase C-theta (PKCΘ). The inhibitory effects of palmitate on the insulin signaling were diminished in PKCΘ- and mTOR (mammalian target of rapamycin)-deficient C2C12 myotubes, and C2C12 myotubes pre-treated with rapamycin. In addition, the phosphorylation of mTOR and p70 ribosomal S6 kinase (S6K) enhanced by palmitate was attenuated in PKCΘ-deficient C2C12 myotubes and in C2C12 myotubes treated with PKCΘ pseudosubstrate. Taken together, our results suggested that palmitate-induced insulin resistance in C2C12 myotubes is mediated by PKCΘ/mTOR/S6K pathway.