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营养不良大鼠骨骼肌中的葡萄糖摄取与葡萄糖转运蛋白

Glucose uptake and glucose transporter proteins in skeletal muscle from undernourished rats.

作者信息

Agote M, Goya L, Ramos S, Alvarez C, Gavete M L, Pascual-Leone A M, Escrivá F

机构信息

Instituto de Bioquímica, Centro Mixto Consejo Superior Investigaciones Científicas Universidad Complutense de Madrid, Facultad Farmacia, Universidad Complutense, Ciudad Universitaria, 28040 Madrid, Spain.

出版信息

Am J Physiol Endocrinol Metab. 2001 Nov;281(5):E1101-9. doi: 10.1152/ajpendo.2001.281.5.E1101.

Abstract

Undernutrition in rats impairs secretion of insulin but maintains glucose normotolerance, because muscle tissue presents an increased insulin-induced glucose uptake. We studied glucose transporters in gastrocnemius muscles from food-restricted and control anesthetized rats under basal and euglycemic hyperinsulinemic conditions. Muscle membranes were prepared by subcellular fractionation in sucrose gradients. Insulin-induced glucose uptake, estimated by a 2-deoxyglucose technique, was increased 4- and 12-fold in control and food-restricted rats, respectively. Muscle insulin receptor was increased, but phosphotyrosine-associated phosphatidylinositol 3-kinase activity stimulated by insulin was lower in undernourished rats, whereas insulin receptor substrate-1 content remained unaltered. The main glucose transporter in the muscle, GLUT-4, was severely reduced albeit more efficiently translocated in response to insulin in food-deprived rats. GLUT-1, GLUT-3, and GLUT-5, minor isoforms in skeletal muscle, were found increased in food-deprived rats. The rise in these minor glucose carriers, as well as the improvement in GLUT-4 recruitment, is probably insufficient to account for the insulin-induced increase in the uptake of glucose in undernourished rats, thereby suggesting possible changes in other steps required for glucose metabolism.

摘要

大鼠营养不良会损害胰岛素分泌,但维持血糖正常耐量,因为肌肉组织胰岛素诱导的葡萄糖摄取增加。我们研究了基础状态和正常血糖高胰岛素血症条件下,食物限制和对照麻醉大鼠腓肠肌中的葡萄糖转运蛋白。通过蔗糖梯度亚细胞分级分离制备肌肉膜。用2-脱氧葡萄糖技术估计,胰岛素诱导的葡萄糖摄取在对照大鼠和食物限制大鼠中分别增加了4倍和12倍。肌肉胰岛素受体增加,但胰岛素刺激的磷酸酪氨酸相关磷脂酰肌醇3激酶活性在营养不良大鼠中较低,而胰岛素受体底物-1含量保持不变。肌肉中的主要葡萄糖转运蛋白GLUT-4严重减少,尽管在食物缺乏大鼠中对胰岛素的反应能更有效地转运。GLUT-1、GLUT-3和GLUT-5是骨骼肌中的次要异构体,在食物缺乏大鼠中增加。这些次要葡萄糖载体的增加以及GLUT-4募集的改善,可能不足以解释营养不良大鼠中胰岛素诱导的葡萄糖摄取增加,从而提示葡萄糖代谢所需其他步骤可能发生了变化。

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