一条新分子信号级联放大反应促进葡萄糖摄取

　　

     生物通报道  哈佛大学锻炼和运动学科系的科学家们发现了一条在锻炼时肌肉中激活的新分子信号。该研究成果发表在《PNAS》杂志上。

    运动锻炼时骨骼肌消耗脂质和糖类。糖类包括储存在肌肉内的糖原和血液中的葡萄糖。作为最主要的葡萄糖代谢组织，骨骼肌是研究促进葡萄糖转运细胞内信号途径的最理想模型。此外，收缩诱导信号刺激葡萄糖转运的机制与胰岛素的利用完全不同。因此对于胰岛素耐受的个体，收缩诱导信号途径是另一种促进葡萄糖吸收的信号途径。对于制药公司来说这条信号途径可作为另一条药物介入调节糖代谢异常的信号途径。

    哥本哈根大学锻炼及运动学科系的研究者与美国哈佛大学乔斯林糖尿病中心的科学家们合作发现了一种新蛋白SNARK，SNARK被证实可在啮齿类和人类骨骼肌发生收缩和运动时被激活。此外利用转基因动物模型在小鼠骨骼肌中过表达失活突变的SNARK，研究者发现与对照组相比实验组收缩诱导的葡萄糖摄取减少了40-50%。

    研究数据表明SNARK可以在肌肉收缩和运动时调控葡萄糖转运，但是它同时证实了有多重信号途径参与调节收缩对葡萄糖转运的激活作用。

（生物通：何嫱）

生物通原文出处推荐
Published online before print August 16, 2010, doi: 10.1073/pnas.1008131107

Sucrose nonfermenting AMPK-related kinase (SNARK) mediates contraction-stimulated glucose transport in mouse skeletal muscle

Ho-Jin Koh, Taro Toyoda, Nobuharu Fujii , Michelle M. Jung, Amee Rathod, R. Jan-Willem Middelbeek, Sarah J. Lessard, Jonas T.Treebak, Katsuya Tsuchihara, Hiroyasu Esumi, Erik A. Richter, Jørgen F. P.Wojtaszewski, Michael F. Hirshman, and Laurie J. Goodyear
The signaling mechanisms that mediate the important effects of contraction to increase glucose transport in skeletal muscle are not well understood, but are known to occur through an insulin-independent mechanism. Muscle-specific knockout of LKB1, an upstream kinase for AMPK and AMPK-related protein kinases, significantly inhibited contraction-stimulated glucose transport. This finding, in conjunction with previous studies of ablated AMPKα2 activity showing no effect on contraction-stimulated glucose transport, suggests that one or more AMPK-related protein kinases are important for this process. Muscle contraction increased sucrose nonfermenting AMPK-related kinase (SNARK) activity, an effect blunted in the muscle-specific LKB1 knockout mice. Expression of a mutant SNARK in mouse tibialis anterior muscle impaired contraction-stimulated, but not insulin-stimulated, glucose transport. Whole-body SNARK heterozygotic knockout mice also had impaired contraction-stimulated glucose transport in skeletal muscle, and knockdown of SNARK in C2C12 muscle cells impaired sorbitol-stimulated glucose transport. SNARK is activated by muscle contraction and is a unique mediator of contraction-stimulated glucose transport in skeletal muscle.