Leucine facilitates the insulin-stimulated glucose uptake and insulin signaling in skeletal muscle cells: involving mTORC1 and mTORC2
Leucine facilitates the insulin-stimulated glucose uptake and insulin signaling in skeletal muscle cells: involving mTORC1 and mTORC2
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亮氨酸促进骨骼肌细胞中胰岛素刺激的葡萄糖摄取和胰岛素信号传导：涉及 mTORC1 和 mTORC2
DOI：
10.1007/s00726-014-1752-9
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发表时间：
2014-08-01
期刊：
影响因子：
3.5
通讯作者：
Yang, Xuefeng
中科院分区：
文献类型：
--
作者：
Liu, Hui;Liu, Rui;Yang, Xuefeng
亮氨酸是一种支链氨基酸，已被证明能促进骨骼肌对葡萄糖的摄取，并增加胰岛素敏感性，但确切的机制仍未确定。在这项研究中，我们在培养的骨骼肌细胞中解决了这个问题。我们的结果表明，亮氨酸单独对葡萄糖摄取或蛋白激酶B(AKT)的磷酸化没有影响，但促进了胰岛素诱导的葡萄糖摄取和AKT的磷酸化。磷脂酰肌醇3-激酶抑制剂Wortmannin可抑制胰岛素刺激的葡萄糖摄取和AKT磷酸化，但这种抑制作用可被亮氨酸部分逆转。哺乳动物靶向雷帕霉素复合体1的抑制剂雷帕霉素对胰岛素刺激的葡萄糖摄取无影响，但可消除亮氨酸对胰岛素刺激的葡萄糖摄取和AKT磷酸化的促进作用。此外，通过用特定的siRNA敲除哺乳动物靶标雷帕霉素复合体2(MTORC2)的核心成分，中和了亮氨酸促进胰岛素诱导的AKT磷酸化。总之，这些发现表明亮氨酸可以通过mTORC1和mTORC2促进胰岛素诱导的胰岛素信号和骨骼肌细胞对葡萄糖的摄取，暗示了这种氨基酸在葡萄糖稳态中的潜在重要性，并提供了新的机制见解。
Leucine, a branched-chain amino acid, has been shown to promote glucose uptake and increase insulin sensitivity in skeletal muscle, but the exact mechanism remains unestablished. We addressed this issue in cultured skeletal muscle cells in this study. Our results showed that leucine alone did not have an effect on glucose uptake or phosphorylation of protein kinase B (AKT), but facilitated the insulin-induced glucose uptake and AKT phosphorylation. The insulin-stimulated glucose uptake and AKT phosphorylation were inhibited by the phosphatidylinositol 3-kinase inhibitor, wortmannin, but the inhibition was partially reversed by leucine. The inhibitor of mammalian target of rapamycin complex 1 (mTORC1), rapamycin, had no effect on the insulin-stimulated glucose uptake, but eliminated the facilitating effect of leucine in the insulin-stimulated glucose uptake and AKT phosphorylation. In addition, leucine facilitation of the insulin-induced AKT phosphorylation was neutralized by knocking down the core component of the mammalian target of rapamycin complex 2 (mTORC2) with specific siRNA. Together, these findings show that leucine can facilitate the insulin-induced insulin signaling and glucose uptake in skeletal muscle cells through both mTORC1 and mTORC2, implicating the potential importance of this amino acid in glucose homeostasis and providing new mechanistic insights.