Institute of Materia Medica, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
Acta Pharmacol Sin. 2010 Jan;31(1):35-42. doi: 10.1038/aps.2009.176. Epub 2009 Dec 21.
To examine the mechanisms underlying the effects of atorvastatin on glucose and lipid metabolism.
Mice with insulin resistance and obesity induced by monosodium glutamate (MSG) were used. Atorvastatin (80 mg.kg(-1).d(-1)) or vehicle control treatment was given orally once a day for 30 days. Plasma levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and free fatty acids were monitored. Serum insulin and glucose concentrations were used to calculate the insulin resistance index and insulin sensitivity index using a homeostasis model. Body length, waistline circumference, intraperitoneal adipose tissue mass, and total body mass were measured. Semi-quantitative RT-PCR and Western analysis were used to determine the expression of inflammatory factors and proteins involved in inflammation signaling pathways.
Atorvastatin improved insulin sensitivity, ameliorated glucose tolerance, and decreased plasma levels of total cholesterol, triglycerides, LDL-C, HDL-C and free fatty acids. Semi-quantitative RT-PCR and Western analysis revealed increased expression of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) in serum and adipose tissue in MSG obese mice. Atorvastatin treatment decreased expression of IL-6, TNF-alpha, nuclear factor kappaB (NF-kappaB) and I-kappa-B (IkappaB) kinase-beta, but increased the expression of IkappaB, in adipose tissue.
Atorvastatin is a potential candidate for the prevention and therapy of diseases associated with insulin resistance such as type 2 diabetes mellitus and cardiovascular disease. One possible mechanism underlying the effects of atorvastatin on glucose and lipid metabolism may be to ameliorate a state of chronic inflammation.
研究阿托伐他汀对糖脂代谢影响的作用机制。
采用谷氨酸单钠（MSG）诱导的胰岛素抵抗肥胖小鼠模型。阿托伐他汀（80mg·kg-1·d-1）或溶剂对照，每日口服 1 次，连续 30 天。监测血浆总胆固醇、甘油三酯、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）和游离脂肪酸水平。血清胰岛素和葡萄糖浓度用于计算胰岛素抵抗指数和胰岛素敏感指数的稳态模型。测量体长、腰围、腹腔内脂肪组织质量和总体重。半定量 RT-PCR 和 Western 分析用于确定炎症因子和炎症信号通路相关蛋白的表达。
阿托伐他汀改善了胰岛素敏感性，改善了葡萄糖耐量，降低了血浆总胆固醇、甘油三酯、LDL-C、HDL-C 和游离脂肪酸水平。半定量 RT-PCR 和 Western 分析显示，MSG 肥胖小鼠血清和脂肪组织中白细胞介素 6（IL-6）和肿瘤坏死因子-α（TNF-α）的表达增加。阿托伐他汀治疗降低了脂肪组织中 IL-6、TNF-α、核因子 kappaB（NF-kappaB）和 I-kappaB 激酶-β的表达，但增加了 IkappaB 的表达。
阿托伐他汀可能是预防和治疗与胰岛素抵抗相关疾病（如 2 型糖尿病和心血管疾病）的候选药物。阿托伐他汀对糖脂代谢影响的作用机制之一可能是改善慢性炎症状态。
