Article Text

PDF

GW23-e1177
ROSUVASTATIN COULD MODULATE INSULIN SIGNALLING AND INHIBIT ATHEROSCLEROSIS
  1. Lv haitao1,
  2. Chi Jufang2,
  3. Liu Longbin2,
  4. Xu Fukang2,
  5. Guo hangyuan2
  1. 1Shaoxing People's Hospital; Wenzhou Medical College
  2. 2Shaoxing People's Hospital

    Abstract

    Objectives To provide evidence that rosuvastatin could improve insulin-resistance and inhibit atherosclerosis by modulating insulin signalling, and whether this effect beyond its plasma cholesterol–lowering effect.

    Methods Thirty-two 6-week-old low-density lipoprotein receptor deficient (LDLR- /-) mice were randomised into four 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 the fasting blood sugar (FBS), fasting insulin (FINS) and total cholesterol (TC); the morphological concentrations of the aorta artery and aorta sinus; the expression of insulin receptor substrate 2(IRS-2), phosphorylated insulin receptor substrate 2 (P-IRS-2), protein kinase B (AKT, also known as PKB) and phosphorylated protein kinase B (P-AKT) in liver.

    Results The HFF diet alone resulted in a plasma FBS concentration of 28.15±1.53 mmol/l and FINS concentration of 1.62±0.07 ng/ml, and administration of rosuvastatin lowered plasma FBS and FINS to 19.99±1.40 mmol/l and 0.79±0.12 ng/ml, while the plasma FBS and FINS levels in HFFR group were partially improved compared to NC group. And administration of rosuvastatin showed a good lipid-lowering effect in HFFR group (33.21±1.12), while this cholesterol-lowering effect of rosuvastatin was significantly reversed by the mevalonic acid in HFFRMA group (39.31±1.57). Furthermore, HFF group had an increase in the morphological concentrations of the aorta artery and aorta sinus, but there was a significant decrease in HFFRMA group and HFFR group. Moreover, there was a high expression of IRS-2, P- IRS-2, AKT and P-AKT in HFFRMA group and HFFR group, but a low expression in HFF group. And there is no significant difference regarding to each afore-mentioned index in HFFR group and HFFRMA group.

    Conclusions Our data show that rosuvastatin could improve insulin-resistance and inhibit atherosclerosis in HFF-fed mice by partially reversing the decrease in the insulin stimulated IRS-2/PI3-K/AKT pathway in liver, and this effect is independent of its cholesterol-lowering effect.

    Statistics from Altmetric.com

    Request permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.