Irisin, a Novel Myokine, Regulates Glucose Uptake in Skeletal Muscle Cells via AMPK
Irisin, a Novel Myokine, Regulates Glucose Uptake in Skeletal Muscle Cells via AMPK
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DOI：
10.1210/me.2014-1353
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发表时间：
2015-06-01
影响因子：
--
通讯作者：
Kim, Hyeon Soo
中科院分区：
文献类型：
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作者：
Lee, Hye Jeong;Lee, Jung Ok;Kim, Hyeon Soo
鸢尾素是一种由骨骼肌产生的新型肌因子。然而，其代谢作用知之甚少。在本研究中，鸢尾素诱导分化的骨骼肌细胞摄取葡萄糖。它增加了AMP激活的蛋白激酶（AMPK）的磷酸化和AMPK的抑制阻断葡萄糖摄取。它还增加了活性氧（ROS）的产生。N-乙酰半胱氨酸，活性氧清除剂，阻断鸢尾素诱导的AMPK磷酸化。此外，鸢尾素激活p38 MAPK的AMPK依赖的方式。抑制和敲低p38 MAPK可阻断鸢尾素诱导的葡萄糖摄取。比色吸光度测定表明，鸢尾素刺激葡萄糖转运蛋白4型的质膜的易位，这种效果被抑制在细胞预处理与p38 MAPK抑制剂或p38 MAPK小干扰RNA。在原代培养的成肌细胞中，鸢尾素增加细胞内钙浓度。STO-609是一种钙/钙调蛋白依赖性蛋白激酶抑制剂，可阻断鸢尾素诱导的AMPK磷酸化，表明钙参与鸢尾素介导的信号传导。我们的研究结果表明，鸢尾素通过ROS介导的AMPK途径在骨骼肌细胞的葡萄糖代谢中发挥重要作用。
Irisin is a novel myokine produced by skeletal muscle. However, its metabolic role is poorly understood. In the present study, irisin induced glucose uptake in differentiated skeletal muscle cells. It increased AMP-activated protein kinase (AMPK) phosphorylation and the inhibition of AMPK blocked glucose uptake. It also increased reactive oxygen species (ROS) generation. N-acetyl cysteine, a ROS scavenger, blocked irisin-induced AMPK phosphorylation. Moreover, irisin activated p38 MAPK in an AMPK-dependent manner. The inhibition and knockdown of p38 MAPK blocked irisin-induced glucose uptake. A colorimetric absorbance assay showed that irisin stimulated the translocation of glucose transporter type 4 to the plasma membrane and that this effect was suppressed in cells pretreated with a p38 MAPK inhibitor or p38 MAPK small interfering RNA. In primary cultured myoblast cells, irisin increased the concentration of intracellular calcium. STO-609, a calcium/calmodulin-dependent protein kinase kinase inhibitor, blocked irisin-induced AMPK phosphorylation, implying that calcium is involved in irisin-mediated signaling. Our results suggest that irisin plays an important role in glucose metabolism via the ROS-mediated AMPK pathway in skeletal muscle cells.