Skeletal muscle glucose transport and metabolism are enhanced in transgenic mice overexpressing the Glut4 glucose transporter.
Skeletal muscle glucose transport and metabolism are enhanced in transgenic mice overexpressing the Glut4 glucose transporter.
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DOI：
10.1074/jbc.270.5.1679
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发表时间：
1995-01
期刊：
影响因子：
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通讯作者：
Polly A. Hansen;E. Gulve;B. Marshall;Jiaping Gao;J. E. Pessin;J. Holloszy;Mike Mueckler
中科院分区：
文献类型：
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作者：
Polly A. Hansen;E. Gulve;B. Marshall;Jiaping Gao;J. E. Pessin;J. Holloszy;Mike Mueckler
在过表达人Glut 4促进葡萄糖转运蛋白的转基因小鼠中研究了骨骼肌葡萄糖转运和代谢。转基因动物的骨骼肌Glut 4蛋白水平相对于其非转基因同窝仔增加了2-4倍。Glut 4过表达增加总转运活性（用1 mM 2-脱氧-D-葡萄糖测量）;这种增加是由于1）基础葡萄糖转运增加（转基因和对照小鼠中0.8 +/- 0.1 vs.0.5 +/- 0.1 μ mol.ml-1.20 min-1，和2）胰岛素刺激的转运增加（在转基因小鼠和对照小鼠中分别为1.5 +/-0.1和0.8 +/-0.1 μ mol.mL-1.20 min-1）。Glut 4过表达也增加了肌肉收缩刺激的葡萄糖转运。此外，与对照组相比，从转基因小鼠分离的肌肉中的糖酵解和葡萄糖掺入糖原的能力增强。这些数据表明，骨骼肌中的Glut 4过表达增加胰岛素和收缩刺激的葡萄糖转运活性和葡萄糖代谢。这些发现与Glut 4作为胰岛素或收缩刺激的主要转运介质的作用一致。
Skeletal muscle glucose transport and metabolism were studied in a line of transgenic mice overexpressing the human Glut4 facilitative glucose transporter. Skeletal muscle Glut4 protein levels were increased 2-4-fold in transgenic animals relative to their nontransgenic litter mates. Glut4 overexpression increased total transport activity (measured with 1 mM 2-deoxy-D-glucose) in the isolated extensor digitorum brevis muscle in the presence of insulin; this increase was due to 1) an increase in basal glucose transport (0.8 +/- 0.1 versus 0.5 +/- 0.1 mumol.ml-1.20 min-1 in transgenic and control mice, respectively) and 2) an increase in insulin-stimulated transport (1.5 +/- 0.1 versus 0.8 +/- 0.1 mumol.ml-1.20 min-1 above basal transport in transgenic and control mice, respectively). Glut4 overexpression also increased glucose transport stimulated by muscle contractions. In addition, glycolysis and glucose incorporation into glycogen were enhanced in muscle isolated from transgenic mice compared to controls. These data demonstrate that Glut4 overexpression in skeletal muscle increases insulin- and contraction-stimulated glucose transport activity and glucose metabolism. These findings are consistent with the role of Glut4 as the primary mediator of transport stimulated by insulin or contractions.