Rosuvastatin may Modulate Insulin Signaling and Inhibit Atherogenesis Beyond its Plasma Cholesterol-Lowering Effect in Insulin-Resistant Mice
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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.
Key wordsRosuvastatin Atherogenesis Insulin signaling Insulin resistance
Low-density lipoprotein receptor deficient
Normal control group
High fat and high fructose diet group
HFF plus rosuvastatin group
HFFR plus mevalonic acid group
3-hydroxy-3-methylglutaryl coenzyme A
Fasting blood sugar
Low-density lipoprotein cholesterol
High-density lipoprotein cholesterol
Insulin receptor substrate 2
Phosphorylated insulin receptor substrate 2
Protein kinase B
Phosphorylated protein kinase B
Glucose transporter 4
Insulin-like growth factors
This study was supported by medical health science and technology plan projects of Zhejiang province, China (Grant No. 2010KYA179); natural science foundation of Zhejiang province, China. (Grant No.Y2100535); shaoxing municipal science and technology plan projects (Grant No. 2010A23010).