Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing City, Zhejiang, 312000, China.
Cardiovasc Drugs Ther. 2012 Oct;26(5):375-82. doi: 10.1007/s10557-012-6406-0.
To provide evidence that rosuvastatin may improve insulin-resistance and inhibit atherogenesis by modulating insulin signaling, and whether this effect occurs beyond its plasma cholesterol-lowering effect.
Thirty-two 6-week-old low-density lipoprotein receptor deficient mice were randomized into 4 groups (n = 8 in each group): Normal control group (NC); High fat and high fructose diet group (HFF); HFF plus rosuvastatin group (HFFR); HFFR plus mevalonic acid group (HFFRMA). After 12 weeks, we measured fasting blood sugar, fasting insulin and cholesterol levels; the morphological concentrations of the aorta and aortic sinus; the expression of insulin receptor substrate 2, phosphorylated insulin receptor substrate 2, protein kinase B, phosphorylated protein kinase B and the glucose transporter 4 in the liver.
Compared with other groups, fasting blood sugar and fasting insulin increased significantly in HFF group. Furthermore, HFF group had an increase in the morphological concentrations of the aorta and aortic sinus, but there was a significant decrease in the HFFRMA group and the HFFR group. Moreover, there was a high expression of insulin receptor substrate 2, phosphorylated insulin receptor substrate 2, protein kinase B, phosphorylated protein kinase B and the glucose transporter 4 in the HFFRMA and HFFR groups, but a low expression in the HFF group. No significant differences regarding each afore-mentioned index was observed in the HFFR and HFFRMA groups.
Our data show that rosuvastatin may improve insulin-resistance and inhibit atherogenesis in HFF-fed mice by partially reversing the decrease in the insulin stimulated insulin receptor substrate 2/Phosphatidylinositol 3-kinase/protein kinase B/glucose transporter 4 pathway in the liver, and that this effect is independent of its cholesterol-lowering effect.
提供证据表明，瑞舒伐他汀可能通过调节胰岛素信号来改善胰岛素抵抗和抑制动脉粥样硬化，并且这种作用是否超出其降低血浆胆固醇的作用。
将 32 只 6 周龄的低密度脂蛋白受体缺陷小鼠随机分为 4 组（每组 8 只）：正常对照组（NC）；高脂肪高果糖饮食组（HFF）；HFF 加瑞舒伐他汀组（HFFR）；HFFR 加甲羟戊酸组（HFFRMA）。12 周后，测量空腹血糖、空腹胰岛素和胆固醇水平；主动脉和主动脉窦的形态浓度；肝脏中胰岛素受体底物 2、磷酸化胰岛素受体底物 2、蛋白激酶 B、磷酸化蛋白激酶 B 和葡萄糖转运体 4 的表达。
与其他组相比，HFF 组空腹血糖和空腹胰岛素明显升高。此外，HFF 组主动脉和主动脉窦的形态浓度增加，但 HFFRMA 组和 HFFR 组明显减少。此外，HFFRMA 和 HFFR 组胰岛素受体底物 2、磷酸化胰岛素受体底物 2、蛋白激酶 B、磷酸化蛋白激酶 B 和葡萄糖转运体 4 的表达较高，但 HFF 组表达较低。HFFR 和 HFFRMA 组之间，上述每个指标均无显著差异。
我们的数据表明，瑞舒伐他汀可能通过部分逆转肝脏中胰岛素刺激的胰岛素受体底物 2/磷脂酰肌醇 3-激酶/蛋白激酶 B/葡萄糖转运体 4 通路的降低，改善 HFF 喂养小鼠的胰岛素抵抗和抑制动脉粥样硬化，并且这种作用独立于其降低胆固醇的作用。
