Sucrose nonfermenting AMPK-related kinase (SNARK) mediates contraction-stimulated glucose transport in mouse skeletal muscle
Sucrose nonfermenting AMPK-related kinase (SNARK) mediates contraction-stimulated glucose transport in mouse skeletal muscle
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DOI：
10.1073/pnas.1008131107
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发表时间：
2010-08-31
影响因子：
11.1
通讯作者：
Goodyear, Laurie J.
中科院分区：
文献类型：
--
作者：
Koh, Ho-Jin;Toyoda, Taro;Goodyear, Laurie J.
收缩对增加骨骼肌葡萄糖转运的重要作用的信号机制还不是很清楚，但已知是通过胰岛素非依赖的机制发生的。肌肉特异性敲除LKB1，一种AMPK和AMPK相关蛋白激酶的上游激酶，显著抑制收缩刺激的葡萄糖运输。这一发现，与先前关于AMPKα2活性消融对收缩刺激的葡萄糖转运没有影响的研究相结合，表明一个或多个AMPK相关的蛋白激酶在这一过程中是重要的。肌肉收缩增加了蔗糖非发酵AMPK相关激酶(SNARK)的活性，这种作用在肌肉特异的LKB1基因敲除小鼠中减弱。突变的snark在小鼠胫骨前肌中的表达损害了收缩刺激的葡萄糖运输，但不影响胰岛素刺激的葡萄糖运输。全身snark杂合子敲除小鼠也有收缩刺激的骨骼肌葡萄糖运输受损，C2C12肌肉细胞中的snark基因敲除也削弱了山梨醇刺激的葡萄糖运输。Snark是由肌肉收缩激活的，是骨骼肌收缩刺激的葡萄糖运输的独特介质。
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 AMPK alpha 2 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.