REGULATION OF GLUCOSE-TRANSPORT IN SKELETAL-MUSCLE
REGULATION OF GLUCOSE-TRANSPORT IN SKELETAL-MUSCLE
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DOI：
10.1096/fasebj.6.14.1426762
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发表时间：
1992-11-01
期刊：
影响因子：
4.8
通讯作者：
YOUNGREN, JF
中科院分区：
文献类型：
--
作者：
BARNARD, RJ;YOUNGREN, JF
葡萄糖进入肌肉细胞主要是通过由蛋白质转运分子组成的载体介导系统实现的。GLUT-1转运蛋白亚型通常存在于肌膜（SL）膜中，并被认为参与基础条件下的葡萄糖转运。在胰岛素刺激下，葡萄糖转运通过将GLUT-4转运蛋白从细胞内库转移到T-小管和SL膜而加速。也可能涉及激活转运蛋白以增加周转次数，但证据远非决定性的。当胰岛素与其受体结合时，它使受体β亚基上的酪氨酸和丝氨酸残基自磷酸化。酪氨酸残基被认为激活酪氨酸激酶，酪氨酸激酶反过来磷酸化/激活未知的第二信使。然而，已报道胰岛素受体抗体增加葡萄糖转运而不增加激酶活性。骨骼肌胰岛素抵抗是肥胖和糖尿病，特别是NIDDM的主要特征。NIDDM患者肌肉中胰岛素受体数量减少，胰岛素激活受体酪氨酸激酶的能力降低。大多数研究报告可转位至SL的GLUT-4转运蛋白的细胞内池无变化。食物的质量和数量都可以调节胰岛素敏感性。高脂肪、精制糖的饮食，类似于典型的美国饮食，与低脂肪、复合碳水化合物的饮食相比，会导致胰岛素抵抗。另一方面，运动增加胰岛素敏感性。急性运动后，肌肉中的葡萄糖转运增加到与最大胰岛素刺激相同的水平。虽然肌膜中GLUT-4转运蛋白的数量随着运动而增加，但胰岛素及其受体均不参与其中。在最初的急性期（可能涉及钙作为激活剂）之后，胰岛素敏感性增加的第二阶段可以在运动后持续长达一天。运动增加胰岛素敏感性的机制尚不清楚。有规律的运动训练也会增加胰岛素敏感性，这可以在最后一次运动后几天记录下来，其机制仍然未知。最近有报道称，随着训练，GLUT-4转运蛋白的肌肉含量增加。尽管在过去的几年里，在了解骨骼肌中葡萄糖转运方面取得了重大进展，但涉及调节转运的机制还远未被理解。
The entry of glucose into muscle cells is achieved primarily via a carrier-mediated system consisting of protein transport molecules. GLUT-1 transporter isoform is normally found in the sarcolemmal (SL) membrane and is thought to be involved in glucose transport under basal conditions. With insulin stimulation, glucose transport is accelerated by translocating GLUT-4 transporters from an intracellular pool out to the T-tubule and SL membranes. Activation of transporters to increase the turnover number may also be involved, but the evidence is far from conclusive. When insulin binds to its receptor, it autophosphorylates tyrosine and serine residues on the beta-subunit of the receptor. The tyrosine residues are thought to activate tyrosine kinases, which in turn phosphorylate/activate as yet unknown second messengers. Insulin receptor antibodies, however, have been reported to increase glucose transport without increasing kinase activity. Insulin resistance in skeletal muscle is a major characteristic of obesity and diabetes mellitus, especially NIDDM. A decrease in the number of insulin receptors and the ability of insulin to activate receptor tyrosine kinase has been documented in muscle from NIDDM patients. Most studies report no change in the intracellular pool of GLUT-4 transporters available for translocation to the SL. Both the quality and quantity of food consumed can regulate insulin sensitivity. A high-fat, refined sugar diet, similar to the typical U.S. diet, causes insulin resistance when compared with a low-fat, complex-carbohydrate diet. On the other hand, exercise increases insulin sensitivity. After an acute bout of exercise, glucose transport in muscle increases to the same level as with maximum insulin stimulation. Although the number of GLUT-4 transporters in the sarcolemma increases with exercise, neither insulin or its receptor is involved. After an initial acute phase, which may involve calcium as the activator, a secondary phase of increased insulin sensitivity can last for up to a day after exercise. The mechanism responsible for the increased insulin sensitivity with exercise is unknown. Regular exercise training also increases insulin sensitivity, which can be documented several days after the final bout of exercise, and again the mechanism is unknown. An increase in the muscle content of GLUT-4 transporters with training has recently been reported. Even though significant progress has been made in the past few years in understanding glucose transport in skeletal muscle, the mechanisms involved in regulating transport are far from being understood.