Glucose metabolism in mice lacking muscle glycogen synthase
Glucose metabolism in mice lacking muscle glycogen synthase
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DOI：
10.2337/diabetes.54.12.3466
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发表时间：
2005-12-01
期刊：
影响因子：
7.7
通讯作者：
Roach, PJ
中科院分区：
文献类型：
--
作者：
Pederson, BA;Schroeder, JM;Roach, PJ
糖原是全身葡萄糖代谢的重要组成部分；MGSKO小鼠由于编码肌糖原合成酶的GYS1基因的破坏而缺乏骨骼肌糖原。MGSKO小鼠比体脂较少的野生型小鼠小5-10%。它们有更多的氧化肌纤维，根据amp激活的蛋白激酶的激活状态，它们有更多的氧化脂肪酸的能力。喂食和禁食的MGSKO小鼠的血糖与野生型小鼠相当。饲喂MGSKO动物血清胰岛素水平较低，而禁食MGSKO动物血清胰岛素水平较低。在葡萄糖耐量试验中，MGSKO小鼠比野生型动物更有效地处理葡萄糖，并且血清胰岛素水平持续升高。这一结果不能用血清乳酸转化增加或肝脏葡萄糖储存增加来解释。然而，尽管肌肉葡萄糖摄取减少，MGSKO小鼠在正糖-高胰岛素钳夹中的葡萄糖输注率是正常的。在钳夹期间，MGSKO动物积累的肝糖原水平明显高于野生型幼崽。尽管GYS1基因的破坏会对肌肉葡萄糖摄取产生负面影响，但总体葡萄糖耐量实际上得到了改善，这可能是因为GYS1在肌肉以外的组织中发挥了作用。
Glycogen is an important component of whole-body glucose metabolism; MGSKO mice lack skeletal muscle glycogen due to disruption of the GYS1 gene, which encodes muscle glycogen synthase. MGSKO mice were 5-10% smaller than wild-type littermates with less body fat. They have more oxidative muscle fibers and, based on the activation state of AMP-activated protein kinase, more capacity to oxidize fatty acids. Blood glucose in fed and fasted MGSKO mice was comparable to wild-type littermates. Serum insulin was lower in fed but not in fasted MGSKO animals. In a glucose tolerance test, MGSKO mice disposed of glucose more effectively than wild-type animals and had a more sustained elevation of serum insulin. This result was not explained by increased conversion to serum lactate or by enhanced storage of glucose in the liver. However, glucose infusion rate in a euglycemic-hyperinsulinemic clamp was normal in MGSKO mice despite diminished muscle glucose uptake. During the clamp, MGSKO animals accumulated significantly higher levels of liver glycogen as compared with wild-type littermates. Although disruption of the GYS1 gene negatively affects muscle glucose uptake, overall glucose tolerance is actually improved, possibly because of a role for GYS1 in tissues other than muscle.