胰島素阻抗與運動訓練的效果－細胞與分子層面之探討

Insulin Resistance and the Effect of Exercise Training-A Molecular and Cellular Approach

簡盟月(Meng-Yueh Chien) ； 吳英黛(Ying-Tai Wu)

《物理治療》 31卷2期 (2006/04) Pp. 130-141

摘要

人體對胰島素敏感度(insulin sensitivity)下降的現象，稱為胰島素阻抗(insulin resistance)，與活動量減少、老化、基因和環境等因素有關，是許多代謝疾病的共同特徵，包括肥胖與第二型糖尿病。本文回顧目前有關胰島素作用調節、造成胰島素阻抗的相關因素，以及運動訓練改善醣類代謝和基因表現的分子機轉。醣類代謝中最重要的步驟是藉由葡萄糖運送蛋白質(glucose transporter 4; GLUT4)轉位(translocation)到細胞膜上，攜帶水溶性的葡萄糖通過脂溶性的細胞膜完成醣類運送(glucose transport)。葡萄糖運送蛋白轉位至細胞膜的過程可透過兩條不同訊息傳遞路徑驅動：一是胰島素訊息傳遞路徑；二是透過缺氧或肌肉收縮誘發腺苷單磷酸活化蛋白質激酶(AMP-activated protein kinase, AMPK)訊息傳遞路徑。第二型糖尿病患者主要是因為透過胰島素接受器(insulin receptor substrate, IRS1, 2)及磷脂醯醇3激酶(phosphatidylinositol 3-kinase, PI3K)的胰島素訊息傳遞路徑損害，以致伴隨骨骼肌胰島素刺激葡萄糖吸收減少，而這些患者的AMPK這條非胰島素訊息傳遞路徑是正常的。越來越多證據指出規律運動可改善胰島素刺激醣類吸收，部分來自於運動改善骨骼肌內調節醣類代謝關鍵蛋白質的活性和基因表現，運動訓練也可誘發AMPK訊息傳遞路徑增加醣類運送。了解胰島素和肌肉收縮活化訊息傳遞路徑的分子機轉有助於第二型糖尿病的防治。

關鍵字

胰島素阻抗 ； 運動 ； 分子機轉

並列摘要

Insulin resistance, resistant to the normal action of insulin, is a progressive metabolic disorder associated with inactivity, aging, genetic predisposition and environmental factors. It is a hallmark feature of a variety of disease states including obesity and metabolic syndrome. This review is focused on current understanding of the molecular mechanisms regulating insulin action and the factors contributing to insulin resistance, and also on the intracellular signaling mechanisms by which exercise training increases glucose metabolism and gene expression in skeletal muscle. Glucose transport, the rate limiting step in glucose metabolism, is mediated by glucose transporter 4 (GLUT4) translocation and can be activated in skeletal muscle by two separate and distinct signaling pathways; one stimulated by insulin and the second by hypoxia or muscle contractions (insulin-independent). Insulin signaling transduction pathway through insulin receptor substrate (IRS)/phosphatidylinositol 3-kinase (PI3K), and glucose transport activity are impaired as a consequence of functional defects in skeletal muscle from Type Ⅱ diabetic patients, whereas insulin-independent pathway major by AMP-activated protein kinase (AMPK) pathway is normal. Evidence is emerging that enhanced insulin-stimulated glucose uptake after exercise training may be partly related to increased expression and activity of key proteins known to regulate glucose metabolism in skeletal muscle. Exercise also leads to an insulin-independent increase in glucose transport mediated by AMPK signaling cascades. Understanding the molecular mechanism for the activation of insulin signaling transduction pathways after exercise training may provide novel entry points for new strategies to enhance glucose metabolism and for improved health in the general population.

並列關鍵字

Insulin resistance ； Exercise ； Molecular mechanism