Rosuvastatin may modulate insulin signaling and inhibit atherogenesis beyond its plasma cholesterol-lowering effect in insulin-resistant mice.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing City, Zhejiang, 312000, China. ghangyuan@hotmail.com
Hangyuan
H
Guo
Haitao
H
Lv
Weiliang
W
Tang
Jufang
J
Chi
Longbin
L
Liu
Fukang
F
Xu
Zheng
Z
Ji
Xiaoya
X
Zhai
Fang
F
Peng
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004032:Diet; D005464:Fluorobenzenes / Q000494:pharmacology / Q000627:therapeutic use*; D005632:Fructose; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*
D005464:Fluorobenzenes; D051275:Glucose Transporter Type 4; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526298:Irs2 protein, mouse; D008055:Lipids; D011743:Pyrimidines; D011973:Receptors, LDL; C495693:Slc2a4 protein, mouse; D013449:Sulfonamides; D005632:Fructose; D000068718:Rosuvastatin Calcium; D051057:Proto-Oncogene Proteins c-akt