Increased glycogen accumulation in transgenic mice overexpressing glycogen synthase in skeletal muscle
Increased glycogen accumulation in transgenic mice overexpressing glycogen synthase in skeletal muscle
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DOI：
10.1073/pnas.93.20.10707
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发表时间：
1996-10-01
影响因子：
11.1
通讯作者：
Lawrence, JC
中科院分区：
文献类型：
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作者：
Manchester, J;Skurat, AV;Lawrence, JC
为了研究糖原合成酶在控制糖原积累中的作用，我们通过使用来自小鼠肌肉肌酸激酶基因的启动子-增强子元件产生了三种转基因小鼠，其中该酶在骨骼肌中过表达。在所有三种品系中，表达在主要由快缩纤维组成的肌肉中最高，如腓肠肌和胫骨前肌。在这些肌肉中，糖原合成酶活性增加了10倍，在糖原含量的增加（最多5倍），尿苷二磷酸葡萄糖浓度显着降低，与糖原合成酶活性的增加一致，这些肌肉中糖原磷酸化酶的水平增加（高达3倍），而胰岛素敏感性葡萄糖转运蛋白4的量保持不变或减少。增加糖原合酶增强糖原积累的观察结果支持糖原合酶的激活，以及葡萄糖转运，有助于响应骨骼肌中的胰岛素而积累糖原。
To investigate the role of glycogen synthase in controlling glycogen accumulation, we generated three lines of transgenic mice in which the enzyme was overexpressed in skeletal muscle by using promoter-enhancer elements derived from the mouse muscle creatine kinase gene, In all three lines, expression was highest in muscles composed primarily of fast-twitch fibers, such as the gastrocnemius and anterior tibialis. In these muscles, glycogen synthase activity was increased by as much as 10-fold, with concomitant increases (up to 5-fold) in the glycogen content, The uridine diphosphoglucose concentrations were markedly decreased, consistent with the increase in glycogen synthase activity, Levels of glycogen phosphorylase in these muscles increased (up to 3-fold), whereas the amount of the insulin-sensitive glucose transporter 4 either remained unchanged or decreased, The observation that increasing glycogen synthase enhances glycogen accumulation supports the conclusion that the activation of glycogen synthase, as well as glucose transport, contributes to the accumulation of glycogen in response to insulin in skeletal muscle.