Insulin signalling, exercise and cellular integrity.
Insulin signalling, exercise and cellular integrity.
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胰岛素信号传导、运动和细胞完整性。
DOI：
10.1042/bst0311281
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发表时间：
2003
影响因子：
3.9
通讯作者：
delAguila,LF
中科院分区：
文献类型：
--
作者：
Kirwan,JP;delAguila,LF
虽然运动对胰岛素敏感性的影响通常是积极的，离心运动提出了一个悖论，因为它会导致胰岛素抵抗的短暂状态，持续长达48小时后的运动回合。过度的离心收缩，如长时间的下坡跑或马拉松跑，会导致肌肉损伤和细胞完整性的破坏。离心运动后，骨骼肌中胰岛素受体酪氨酸磷酸化和胰岛素信号通路中的后续步骤，包括胰岛素受体底物-1（IRS-1）相关磷酸肌醇3-激酶（PI 3 K）、Akt激酶丝氨酸磷酸化和活性以及葡萄糖转运蛋白（GLUT-4）蛋白含量的下调是明显的。此外，单核细胞分泌的肿瘤坏死因子α（TNF-α）增加与这种类型的运动后PI 3 K活性降低相关。最近的研究表明，TNF-α可以增加IRS-1丝氨酸/苏氨酸磷酸化，这会损害IRS-1与胰岛素受体的对接，从而抑制胰岛素信号传导。因此，解释离心运动后胰岛素抵抗的统一假设可能包括肌肉细胞完整性破坏引起的炎症，导致包括TNF-α在内的急性期反应，后者抑制胰岛素信号传导和随后的代谢事件。相反，运动训练增加胰岛素信号和GLUT-4表达，降低骨骼肌中TNF-α表达，并与胰岛素敏感性增强相关。这些观察结果突出了细胞和分子适应运动的复杂性。了解这些适应是必不可少的，以建立一个良好的理论基础，推荐运动作为胰岛素抵抗和2型糖尿病的治疗干预。
Although the effects of exercise on insulin sensitivity are generally positive, eccentric exercise presents a paradox because it induces a transient state of insulin resistance that persists for up to 48 h after the exercise bout. Excessive eccentric contractions, such as prolonged downhill running, or marathon running, causes muscle damage and disruption of the integrity of the cell. Down-regulation of insulin receptor tyrosine phosphorylation and subsequent steps in the insulin signalling pathway, including insulin receptor substrate-1 (IRS-1)-associated phosphoinositide 3-kinase (PI3K), Akt kinase serine phosphorylation and activity and glucose transporter (GLUT-4) protein content, are evident in skeletal muscle after eccentric exercise. Furthermore, increased tumour necrosis factor α (TNF-α) secretion from monocytes is associated with the decrease in PI3K activity after this type of exercise. Recent studies have shown that TNF-α can increase IRS-1 serine/threonine phosphorylation, which impairs IRS-1 docking to the insulin receptor, and this inhibits insulin signalling. Thus a unifying hypothesis to explain insulin resistance after eccentric exercise may include inflammation arising from the disruption of muscle-cell integrity, leading to an acute-phase response that includes TNF-α, with the latter inhibiting insulin signalling and subsequent metabolic events. In contrast, exercise training increases insulin signalling and GLUT-4 expression, decreases TNF-α expression in skeletal muscle, and is associated with enhanced insulin sensitivity. These observations highlight the complexity of the cellular and molecular adaptations to exercise. Understanding these adaptations is essential in order to establish a sound theoretical basis for recommending exercise as a therapeutic intervention for insulin resistance and type 2 diabetes.