Wang X, Yu W, Nawaz A, Guan F, Sun S, Wang C
Department of Pathophysiology, Yunyang Medical College, Shiyan, China.
Exp Clin Endocrinol Diabetes. 2010 Oct;118(9):657-61. doi: 10.1055/s-0030-1252069. Epub 2010 Apr 28.
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.
棕榈酸酯诱导骨骼肌细胞胰岛素抵抗的潜在机制尚不清楚。在本研究中，我们发现棕榈酸酯抑制C2C12肌管中的胰岛素信号传导，同时蛋白激酶C-θ（PKCΘ）的磷酸化增强。在PKCΘ和雷帕霉素靶蛋白（mTOR）缺陷的C2C12肌管以及用雷帕霉素预处理的C2C12肌管中，棕榈酸酯对胰岛素信号传导的抑制作用减弱。此外，在PKCΘ缺陷的C2C12肌管和用PKCΘ假底物处理的C2C12肌管中，棕榈酸酯增强的mTOR和p70核糖体S6激酶（S6K）的磷酸化减弱。综上所述，我们的结果表明，棕榈酸酯诱导的C2C12肌管胰岛素抵抗是由PKCΘ/mTOR/S6K途径介导的。
