Effect of pravastatin on the development of diabetes and adiponectin production
Effect of pravastatin on the development of diabetes and adiponectin production
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DOI：
10.1016/j.atherosclerosis.2007.02.013
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发表时间：
2008-01-01
期刊：
影响因子：
5.3
通讯作者：
Shimomura, Iichiro
中科院分区：
文献类型：
--
作者：
Takagi, Toshiyuki;Matsuda, Morihiro;Shimomura, Iichiro
在苏格兰西部冠状动脉预防研究（WOSCOPS）中，使用3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂普伐他汀治疗高胆固醇血症男性，使其进展为糖尿病的可能性降低30%。然而，普伐他汀的这种作用的机制尚未研究。在本研究中，我们研究了普伐他汀对肥胖糖尿病小鼠糖尿病发展的影响，以及对胰岛素诱导的葡萄糖摄取和脂联素产生的影响。普伐他汀治疗减弱了db/db和高脂肪/高糖饲料喂养的C57 BL/6 J小鼠的糖尿病发展。体内葡萄糖转运试验表明，普伐他汀上调脂肪组织的葡萄糖摄取。从普伐他汀处理的小鼠中分离的原代脂肪细胞中胰岛素刺激的葡萄糖摄取增强。普伐他汀处理增加3 T3-L1脂肪细胞中脂联素的产生。血浆脂联素水平显着增加普伐他汀治疗的小鼠。来自WOSCOPS生物库的血浆样本分析表明，普伐他汀治疗后血浆脂联素水平显著增加（安慰剂-0.28 +/-0.34 μ g/ml vs普伐他汀+1.47 +/-0.33 μ g/ml，p = 0.0003）。总之，我们的研究结果表明，普伐他汀可能对脂肪组织有有益的影响，这可能部分解释了普伐他汀治疗减少糖尿病的发展。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
In the West of Scotland Coronary Prevention Study (WOSCOPS), treatment of hypercholesterolemic men with pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, reduced their likelihood to progress to diabetes mellitus by 30%. However, the mechanism of this effect of pravastatin has not been investigated. In the current study, we examined the effect of pravastatin on the development of diabetes in obese diabetic mice, and on the insulin-induced glucose uptake and adiponectin production. Pravastatin treatment attenuated the development of diabetes in db/db and high fat/high sucrose diet-fed C57BL/6J mice. An in vivo glucose transport assay showed that pravastatin upregulated glucose uptake in adipose tissue. Insulin-stimulated glucose uptake was enhanced in primary adipocytes isolated from pravastatin-treated mice. Pravastatin treatment increased adiponectin production in 3T3-L1 adipocytes. Plasma adiponectin levels were significantly increased in pravastatin-treated mice. Analyses of plasma samples from the WOSCOPS biobank indicated a significant increase of plasma adiponectin levels with pravastatin treatment (placebo -0.28 +/- 0.34 mu g/ml versus pravastatin +1.47 +/- 0.33 mu g/ml, p = 0.0003). Taken together, our findings suggest that pravastatin may have beneficial effects on adipose tissue, which may partly explain the reduction of the development of diabetes by pravastatin treatment. (C) 2007 Elsevier Ireland Ltd. All rights reserved.