Acarbose ameliorates atherogenecity of low-density lipoprotein in patients with impaired glucose tolerance
Acarbose ameliorates atherogenecity of low-density lipoprotein in patients with impaired glucose tolerance
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DOI：
10.1016/j.metabol.2006.03.002
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发表时间：
2006-07-01
影响因子：
9.8
通讯作者：
Katayama, Shigehiro
中科院分区：
文献类型：
--
作者：
Inoue, Ikuo;Shinoda, Yuichi;Katayama, Shigehiro
阿卡波糖是一种α-葡萄糖苷酶抑制剂，用于控制血糖水平。该药物还可以降低心血管疾病的风险，但其潜在机制仍有待阐明。因此，我们假设阿卡波糖治疗可以改善低密度脂蛋白(LDL)的致动脉粥样硬化能力，低密度脂蛋白是动脉粥样硬化形成中的关键分子。糖耐量低减患者接受或不给予阿卡波糖治疗(阿卡波糖治疗组和对照组各20例)，饮食治疗3个月。在CuSO4存在下，通过测量双烯形成的滞后时间来确定低密度脂蛋白的氧化敏感性。阿卡波糖组治疗前的滞后时间明显长于对照组。此外，密度梯度脂蛋白分离和盘状聚丙烯酰胺凝胶电泳分析表明，阿卡波糖减少了小而致密的低密度脂蛋白的数量，低密度脂蛋白是一种更容易导致动脉粥样硬化和氧化的低密度脂蛋白。我们还发现治疗后低密度脂蛋白的脂肪酸组成发生了变化：阿卡波糖组低密度脂蛋白中预防心血管疾病的有益物质--多不饱和脂肪酸(omega-3)显著增加，饱和脂肪酸和甘油三酯降低。目前的研究结果表明，阿卡波糖治疗通过改善低密度脂蛋白的动脉粥样硬化来降低心血管疾病的风险。(C)2006 Elsevier Inc.保留所有权利。
Acarbose, alpha-glucosidase inhibitor, is administered to control blood glucose levels. The drug also reduces the risk of cardiovascular disease, but the underlying mechanism is still to be elucidated. We therefore hypothesized that treatment with acarbose ameliorates the atherogenecity of low-density lipoprotein (LDL), a key molecule in atherogenesis. Patients with impaired glucose tolerance were or were not treated with acarbose (acarbose-treated group [n = 20] and control group [n = 20], respectively) for 3 months under dietary therapy. The oxidative susceptibility of LDL was determined by measuring lag time for the formation of dienes in the presence of CuSO4. The lag time was significantly longer in the acarbose-treated group than in the control group before treatment. Moreover, the density gradient lipoprotein separation and disk polyacrylamide gel electrophoresis analyses showed that acarbose reduced the amount of small dense LDL, a more atherogenic and oxidatively susceptible form of LDL. We also found that the fatty acid composition of LDL changed after the treatment: polyunsaturated (omega-3) fatty acid, a beneficial substance for preventing cardiovascular disease, was significantly increased, whereas saturated fatty acids and triglyceride were decreased in the LDL of the acarbose-treated group. The present findings suggest that acarbose treatment reduces the risk of cardiovascular diseases by ameliorating the atherogenecity of LDL. (c) 2006 Elsevier Inc. All rights reserved.