PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance.
PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance.
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DOI：
10.1172/jci17975
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发表时间：
2003-05
期刊：
影响因子：
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通讯作者：
S. Crosson;Ahmir H. Khan;J. Printen;J. Pessin;A. Saltiel
中科院分区：
文献类型：
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作者：
S. Crosson;Ahmir H. Khan;J. Printen;J. Pessin;A. Saltiel
蛋白质靶向糖原（PTG）是一种支架蛋白，它将蛋白磷酸酶1 α（PP1 α）靶向糖原，并将其与参与糖原合成和降解的酶连接起来。我们产生了具有PTG基因杂合缺失的小鼠。这些小鼠在脂肪组织、肝脏、心脏和骨骼肌中的糖原储存减少，对应于降低的糖原合成酶活性和糖原合成速率。尽管年轻的PTG杂合子小鼠最初表现出正常的葡萄糖耐量，但随着年龄的增长，葡萄糖耐受不良、高胰岛素血症和胰岛素抵抗会逐渐发展。老年PTG杂合子小鼠的胰岛素抵抗与肌肉甘油三酯含量的显著增加相关，胰岛素受体信号转导相应减弱。这些数据表明，PTG在糖原合成中起着关键作用，并且对于维持糖原和脂质之间燃料底物的分配的适当代谢平衡是必要的。
Protein targeting to glycogen (PTG) is a scaffolding protein that targets protein phosphatase 1alpha (PP1alpha) to glycogen, and links it to enzymes involved in glycogen synthesis and degradation. We generated mice that possess a heterozygous deletion of the PTG gene. These mice have reduced glycogen stores in adipose tissue, liver, heart, and skeletal muscle, corresponding with decreased glycogen synthase activity and glycogen synthesis rate. Although young PTG heterozygous mice initially demonstrate normal glucose tolerance, progressive glucose intolerance, hyperinsulinemia, and insulin resistance develop with aging. Insulin resistance in older PTG heterozygous mice correlates with a significant increase in muscle triglyceride content, with a corresponding attenuation of insulin receptor signaling. These data suggest that PTG plays a critical role in glycogen synthesis and is necessary to maintain the appropriate metabolic balance for the partitioning of fuel substrates between glycogen and lipid.