Lee Hye Jeong, Lee Jung Ok, Kim Nami, Kim Joong Kwan, Kim Hyung Ip, Lee Yong Woo, Kim Su Jin, Choi Jong-Il, Oh Yoonji, Kim Jeong Hyun, Park Sun Hwa, Kim Hyeon Soo
Department of Anatomy (H.J.L., J.O.L., N.K., J.K.K., H.I.K., Y.W.L., S.J.K., S.H.P., H.S.K.), Korea University College of Medicine, Seoul, Korea 136-705; Division of Cardiology (J.-I.C.), Department of Internal Medicine, Korea University Medical Center, Seoul, Korea; College of Nursing (Y.O.), Korea University, Seoul, Korea 136-705; College of Pre-Pharm·Med (J.H.K.), DukSung Women's University, Seoul, Korea 132-714; and College of Pharmacy (S.-H.), University of Rhode Island, Kingston, Rhode Island 02881.
Mol Endocrinol. 2015 Jun;29(6):873-81. doi: 10.1210/me.2014-1353. Epub 2015 Mar 31.
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.
鸢尾素是一种由骨骼肌产生的新型肌动蛋白。然而，其代谢作用尚不清楚。在本研究中，鸢尾素可诱导分化的骨骼肌细胞摄取葡萄糖。它增加了腺苷酸活化蛋白激酶（AMPK）的磷酸化，而对AMPK的抑制则阻断了葡萄糖摄取。它还增加了活性氧（ROS）的生成。ROS清除剂N-乙酰半胱氨酸可阻断鸢尾素诱导的AMPK磷酸化。此外，鸢尾素以AMPK依赖的方式激活p38丝裂原活化蛋白激酶（p38 MAPK）。对p38 MAPK的抑制和敲低可阻断鸢尾素诱导的葡萄糖摄取。比色吸光度测定表明，鸢尾素可刺激4型葡萄糖转运体向质膜的转位，而在用p38 MAPK抑制剂或p38 MAPK小干扰RNA预处理的细胞中，这种作用受到抑制。在原代培养的成肌细胞中，鸢尾素增加了细胞内钙的浓度。钙/钙调蛋白依赖性蛋白激酶激酶抑制剂STO-609可阻断鸢尾素诱导的AMPK磷酸化，这意味着钙参与了鸢尾素介导的信号传导。我们的结果表明，鸢尾素通过骨骼肌细胞中ROS介导的AMPK途径在葡萄糖代谢中发挥重要作用。
