Atorvastatin delays the glucose clearance rate in hypercholesterolemic rabbits
Atorvastatin delays the glucose clearance rate in hypercholesterolemic rabbits
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阿托伐他汀可延迟高胆固醇血症兔的葡萄糖清除率。
DOI：
10.1016/j.biopha.2015.03.007
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发表时间：
2015-05-01
影响因子：
7.5
通讯作者：
Liu, Enqi
中科院分区：
文献类型：
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作者：
Cheng, Daxin;Wang, Yanli;Liu, Enqi
基于最近的临床证据，他汀类药物可能增加高胆固醇血症患者新发糖尿病的风险。然而，因果关系必须在动物实验中澄清和证实。因此，我们通过给兔子喂高胆固醇饮食（HCD）来模拟高胆固醇血症，并进行16周的阿托伐他汀给药，以研究他汀对葡萄糖代谢的影响。静脉内葡萄糖耐量试验显示，他汀类药物治疗家兔的血糖水平始终较高，并且血液中葡萄糖清除率低于HCD家兔。他汀类药物治疗兔的葡萄糖曲线下面积增量也显著大于HCD兔。但静脉胰岛素耐量试验两组间无显著性差异。外源性胰岛素的降糖能力不受他汀类药物治疗高胆固醇血症兔。单次给予他汀类药物对正常家兔的糖代谢无影响。他汀类药物还显着增加高密度脂蛋白胆固醇，丙氨酸氨基转移酶和天冬氨酸氨基转移酶的水平，并降低血浆总胆固醇，甘油三酯和低密度脂蛋白胆固醇在高胆固醇血症兔的水平，而它不影响血糖和胰岛素的血浆水平。目前的结果表明，阿托伐他汀治疗导致显着延迟的葡萄糖清除在高胆固醇血症兔，这种兔模型可以适用于研究他汀类药物对糖代谢的影响。(C)2015年Elsevier Masson SAS。All rights reserved.
The administration of statin might increase the risk of new-onset diabetes in hypercholesterolemic patients based on the recent clinical evidence. However, the causal relationship must be clarified and confirmed in animal experiments. Therefore, we mimicked hypercholesterolemia by feeding rabbits a high-cholesterol diet (HCD) and performed 16 weeks of atorvastatin administration to investigate the effect of statin on glucose metabolism. The intravenous glucose tolerance test showed that plasma glucose levels in the statin-treated rabbits were consistently higher and that there was a slower rate of glucose clearance from the blood than in HCD rabbits. The incremental area under the curve for glucose in the statin-treated rabbits was also significantly larger than in the HCD rabbits. However, there was no significant difference between the two groups in the intravenous insulin tolerance test. The glucose-lowering ability of exogenous insulin was not impaired by statin treatment in hypercholesterolemic rabbits. The administration of a single dose of statin did not affect glucose metabolism in normal rabbits. The statin also significantly increased the levels of high-density lipoprotein cholesterol, alanine aminotransferase and aspartate transaminase and decreased plasma levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol in the hypercholesterolemic rabbits, whereas it did not affect plasma levels of glucose and insulin. The current results showed that atorvastatin treatment resulted in a significant delay of glucose clearance in hypercholesterolemic rabbits, and this rabbit model could be suitable for studying the effects of statin on glucose metabolism. (C) 2015 Elsevier Masson SAS. All rights reserved.