The muscle-specific protein phosphatase PP1G/RGL(GM) is essential for activation of glycogen synthase by exercise
The muscle-specific protein phosphatase PP1G/RGL(GM) is essential for activation of glycogen synthase by exercise
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DOI：
10.1074/jbc.m105518200
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发表时间：
2001-10-26
影响因子：
4.8
通讯作者：
DePaoli-Roach, AA
中科院分区：
文献类型：
--
作者：
Aschenbach, WG;Suzuki, Y;DePaoli-Roach, AA
在骨骼肌中，胰岛素和收缩活动都是糖原合成的生理刺激，这被认为部分是由于糖原合成酶（GS）的去磷酸化和激活。PP1G/R-GL（G(M)）是一种糖原/肌浆网相关的I型磷酸酶，最初被认为介导胰岛素对糖原代谢的控制。然而，我们最近发现（Suzuki， Y., Lanner， C., Kim， J.-H.）， Vilardo， P. G, Zhang， H., Yang Jie， J, Cooper， L. D, Steele， M, Kennedy， A., Bock， C., Scrimgeour， A., Lawrence， J. C. Jr.， L.和DePaoli-Roach， A. A. (2001) Mol. Cell。与野生型（WT）相似，胰岛素激活R-GL（G(M)）敲除（KO）小鼠肌肉中的GS。为了确定PP1G是否参与肌肉收缩过程中的糖原代谢，我们对RGL KO和过表达者（OE）进行了两种收缩模型，即体内跑步机运动和原位电刺激。这两种方法都使WT小鼠的GS -/+葡萄糖-6- p活性比增加了2倍，但在KO小鼠中完全没有这种反应。KO小鼠，其GS活性降低与基础糖原水平显著降低相关，表现出最大运动能力受损，但收缩诱导的葡萄糖运输激活未受影响。R-GL OE小鼠的特点是GS活性比增强，骨骼肌糖原含量增加3-4倍。这些动物能够正常耐受运动。肌肉收缩后的GS刺激和葡萄糖摄取与WT幼崽相比无显著差异。这些结果表明，虽然PP1G/R-GL不是胰岛素激活GS所必需的，但它对基础条件下糖原代谢的调节和对收缩活动的反应是必需的，这可能解释了尽管胰岛素正常激活GS，但R-GL KO小鼠肌糖原含量降低。
In skeletal muscle both insulin and contractile activity are physiological stimuli for glycogen synthesis, which is thought to result in part from the dephosphorylation and activation of glycogen synthase (GS). PP1G/R-GL(G(M)) is a glycogen/sarcoplasmic reticulum-associated type I phosphatase that was originally postulated to mediate insulin control of glycogen metabolism. However, we recently showed (Suzuki, Y., Lanner, C., Kim, J.-H., Vilardo, P. G., Zhang, H., Jie Yang, J., Cooper, L. D., Steele, M., Kennedy, A., Bock, C., Scrimgeour, A., Lawrence, J. C. Jr., L., and DePaoli-Roach, A. A. (2001) Mol. Cell. Biol. 21, 2683-2694) that insulin activates GS in muscle of R-GL(G(M)) knockout (KO) mice similarly to the wild type (WT). To determine whether PP1G is involved in glycogen metabolism during muscle contractions, RGL KO and overexpressors (OE) were subjected to two models of contraction, in vivo treadmill running and in situ electrical stimulation. Both procedures resulted in a 2-fold increase in the GS -/+ glucose-6-P activity ratio in WT mice, but this response was completely absent in the KO mice. The KO mice, which also have a reduced GS activity associated with significantly reduced basal glycogen levels, exhibited impaired maximal exercise capacity, but contraction-induced activation of glucose transport was unaffected. The R-GL OE mice are characterized by enhanced GS activity ratio and an similar to3-4-fold increase in glycogen content in skeletal muscle. These animals were able to tolerate exercise normally. Stimulation of GS and glucose uptake following muscle contraction was not significantly different as compared with WT littermates. These results indicate that although PP1G/R-GL is not necessary for activation of GS by insulin, it is essential for regulation of glycogen metabolism under basal conditions and in response to contractile activity, and may explain the reduced muscle glycogen content in the R-GL KO mice, despite the normal insulin activation of GS.