Overexpression of Interleukin-15 exhibits improved glucose tolerance and promotes GLUT4 translocation via AMP-Activated protein kinase pathway in skeletal muscle
Overexpression of Interleukin-15 exhibits improved glucose tolerance and promotes GLUT4 translocation via AMP-Activated protein kinase pathway in skeletal muscle
复制标题
DOI：
10.1016/j.bbrc.2019.01.024
复制
发表时间：
2019-02-19
影响因子：
3.1
通讯作者：
Rakugi, Hiromi
中科院分区：
文献类型：
--
作者：
Fujimoto, Taku;Sugimoto, Ken;Rakugi, Hiromi
骨骼肌完成了体内80%的葡萄糖代谢。由于改善了骨骼肌的葡萄糖摄取，习惯性运动被认为是有益的，可以改善胰岛素抵抗和预防糖尿病。研究骨骼肌调节葡萄糖摄取的机制有助于糖尿病的预防和治疗。肌因子是骨骼肌分泌的一种细胞因子，具有调节肌肉代谢的作用。据报道，白细胞介素-15 （IL-15）是一种能在体外改善葡萄糖代谢的肌因子，但其机制尚不清楚。本研究通过检测骨骼肌特异性IL-15转基因小鼠（IL-15TG）的糖代谢，探讨IL-15对骨骼肌糖代谢的影响。虽然高脂饮食喂养的IL-15TG在腹腔胰岛素耐量试验中没有明显差异，但与野生型C57BL/6相比，它们的葡萄糖耐量受损程度较低。在IL-15TG的骨骼肌中，amp活化蛋白激酶（AMPK）、160 kDa的Akt底物（AS160）、tre2 /USP6、BUB2和cdc16结构域家族成员1 （TBC1D1）的磷酸化和葡萄糖转运蛋白4型（GLUT4）的易位加速。我们的研究表明，IL-15在骨骼肌中的过表达通过AMPK途径改善骨骼肌的葡萄糖代谢。我们首次报道了IL-15在肌肉糖代谢中的信号通路的体内研究，从而有助于阐明肌因子对肌肉糖代谢的调节机制。(C) 2019 Elsevier Inc.版权所有。
Skeletal muscle performs 80% of the glucose metabolism in the body. Improvement of insulin resistance and prevention of diabetes by habitual exercise is considered beneficial due to the improved glucose uptake in skeletal muscles. Investigation of the mechanism by which skeletal muscles regulate glucose uptake can contribute to the prevention and treatment of diabetes. Myokines are a kind of cytokine secreted from skeletal muscle, which are expected to regulate muscle metabolism. Interleukin-15 (IL-15) is one such myokine that has been reported to improve glucose metabolism in vitro, although the mechanism remains unclear. In this study, we examined the glucose metabolism of skeletal muscle specific IL-15 transgenic mice (IL-15TG), and investigated how IL-15 affects glucose metabolism in skeletal muscles. Although High Fat Diet-fed IL-15TG did not exhibit obvious difference in intraperitoneal insulin tolerance test, they had less impaired glucose tolerance compared to wild-type C57BL/6. Phosphorylation of AMP-activated protein kinase (AMPK), Akt substrate of 160 kDa (AS160), tre-2/USP6, BUB2, and cdc16 domain family member 1 (TBC1D1), and translocation of Glucose transporter type 4 (GLUT4) were accelerated in the skeletal muscle of IL-15TG. Our study demonstrated that overexpression of IL-15 in skeletal muscle improves glucose metabolism in skeletal muscle via AMPK pathway. We report the first in-vivo study that describes the signaling pathway of IL-15 in muscle glucose metabolism, and thereby contributes to the elucidation of the regulatory mechanism of muscle glucose metabolism by myokines. (C) 2019 Elsevier Inc. All rights reserved.