Barnard R J, Youngren J F
Department of Physiological Science, University of California, Los Angeles 90024-1527.
FASEB J. 1992 Nov;6(14):3238-44. doi: 10.1096/fasebj.6.14.1426762.
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.
葡萄糖进入肌肉细胞主要是通过一个由蛋白质转运分子组成的载体介导系统来实现的。GLUT-1转运体异构体通常存在于肌膜（SL）膜中，被认为在基础条件下参与葡萄糖转运。在胰岛素刺激下，通过将GLUT-4转运体从细胞内池转运到T小管和SL膜上，葡萄糖转运得以加速。转运体的激活以增加转换数可能也有参与，但证据远非确凿。当胰岛素与其受体结合时，它会使受体β亚基上的酪氨酸和丝氨酸残基发生自身磷酸化。酪氨酸残基被认为会激活酪氨酸激酶，酪氨酸激酶进而磷酸化/激活尚不清楚的第二信使。然而，据报道胰岛素受体抗体可增加葡萄糖转运而不增加激酶活性。骨骼肌中的胰岛素抵抗是肥胖症和糖尿病尤其是非胰岛素依赖型糖尿病的主要特征。在非胰岛素依赖型糖尿病患者的肌肉中，已证实胰岛素受体数量减少以及胰岛素激活受体酪氨酸激酶的能力下降。大多数研究报告称，可供转运到SL的GLUT-4转运体的细胞内池没有变化。所摄入食物的质量和数量都能调节胰岛素敏感性。与典型的美国饮食类似的高脂肪、精制糖饮食与低脂、复合碳水化合物饮食相比会导致胰岛素抵抗。另一方面，运动可增加胰岛素敏感性。一次急性运动后，肌肉中的葡萄糖转运增加到与最大胰岛素刺激时相同的水平。虽然肌膜中GLUT-4转运体的数量会随着运动增加，但这一过程既不涉及胰岛素也不涉及胰岛素受体。在最初的急性期（可能涉及钙作为激活剂）之后，运动后胰岛素敏感性增加的第二阶段可持续长达一天。运动导致胰岛素敏感性增加的机制尚不清楚。定期运动训练也会增加胰岛素敏感性，这在最后一次运动后的几天就可以得到证实，其机制同样未知。最近有报道称训练会使肌肉中GLUT-4转运体的含量增加。尽管在过去几年中，在理解骨骼肌中的葡萄糖转运方面取得了重大进展，但调节转运的机制仍远未被理解。
