α-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle
α-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle
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DOI：
10.1016/j.bbrc.2005.05.035
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发表时间：
2005-07-08
影响因子：
3.1
通讯作者：
Park, JY
中科院分区：
文献类型：
--
作者：
Lee, WJ;Song, KH;Park, JY
甘油三酯在骨骼肌中的积累有助于肥胖症的胰岛素抵抗。我们最近发现，α-硫辛酸（ALA）通过减少非脂肪组织中甘油三酯的积累，降低了糖尿病易感性肥胖大鼠的体重，并预防了糖尿病的发展。AMP活化蛋白激酶（AMPK）是细胞能量代谢的主要调节因子。我们研究了ALA是否通过激活AMPK降低骨骼肌中甘油三酯的积累。与对照大鼠相比，肥胖大鼠的α 2-AMPK活性降低。给肥胖大鼠施用ALA增加了全身和骨骼肌中胰岛素刺激的葡萄糖处置。ALA还增加脂肪酸氧化和激活AMPK在骨骼肌。腺病毒介导的显性负性AMPK给药到骨骼肌阻止ALA诱导的脂肪酸氧化和胰岛素刺激的葡萄糖摄取增加。这些结果表明，ALA诱导的胰岛素敏感性的改善是通过激活AMPK和减少骨骼肌中甘油三酯的积累介导的。(c)2005年由Elsevier Inc.出版
Triglyceride accumulation in skeletal muscle contributes to insulin resistance in obesity. We recently showed that alpha-lipoic acid (ALA) reduces body weight and prevents the development of diabetes in diabetes-prone obese rats by reducing triglyceride accumulation in non-adipose tissues. AMP-activated protein kinase (AMPK) is a major regulator of cellular energy metabolism. We examined whether ALA lowers triglyceride accumulation in skeletal muscle by activating AMPK. alpha 2-AMPK activity was decreased in obese rats compared to control rats. Administration of ALA to obese rats increased insulin-stimulated glucose disposal in whole body and in skeletal muscle. ALA also increased fatty acid oxidation and activated AMPK in skeletal muscle. Adenovirus-mediated administration of dominant negative AMPK into skeletal muscle prevented the ALA-induced increases in fatty acid oxidation and insulin-stimulated glucose uptake. These results suggest that ALA-induced improvement of insulin sensitivity is mediated by activation of AMPK and reduced triglyceride accumulation in skeletal muscle. (c) 2005 Published by Elsevier Inc.