Cardiovascular Drugs and Therapy

, Volume 26, Issue 5, pp 375–382 | Cite as

Rosuvastatin may Modulate Insulin Signaling and Inhibit Atherogenesis Beyond its Plasma Cholesterol-Lowering Effect in Insulin-Resistant Mice

  • Hangyuan Guo
  • Haitao Lv
  • Weiliang Tang
  • Jufang Chi
  • Longbin Liu
  • Fukang Xu
  • Zheng Ji
  • Xiaoya Zhai
  • Fang Peng



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 words

Rosuvastatin Atherogenesis Insulin signaling Insulin resistance 



Low-density lipoprotein


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




Total cholesterol


Low-density lipoprotein cholesterol


High-density lipoprotein cholesterol


Fasting insulin


Insulin resistance


Insulin receptor substrate 2


Phosphorylated insulin receptor substrate 2


Protein kinase B


Phosphorylated protein kinase B


Glucose transporter 4


Phosphatidylinositol 3-kinase


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).


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Hangyuan Guo
    • 1
  • Haitao Lv
    • 1
    • 2
  • Weiliang Tang
    • 1
  • Jufang Chi
    • 1
  • Longbin Liu
    • 1
  • Fukang Xu
    • 1
  • Zheng Ji
    • 1
    • 2
  • Xiaoya Zhai
    • 1
    • 2
  • Fang Peng
    • 1
  1. 1.Department of Cardiology, Shaoxing People’s HospitalShaoxing Hospital of Zhejiang UniversityShaoxing CityChina
  2. 2.Wenzhou Medical CollegeWenzhou CityChina

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