Abstract

BACKGROUND: The aim of this study was to investigate the effects of different statins on glucose uptake and to confirm its mechanism in primary cultured rat cardiomyocytes after administration of atorvastatin, pravastatin, and rosuvastatin.

MATERIAL AND METHODS: Primary cultured rat cardiomyocytes were randomly assigned to 5 groups: normal control group (OB), insulin group (S1), statin 1-μM (S2), 5-μM (S3), and 10-μM (S4) groups for 3 different statins. The 2-[3H]-DG uptake of each group was determined and the mRNA and protein expression levels of glucose transporter type 4 (GLUT4), insulin receptor substrate (IRs), and RhoA were assessed.

RESULTS: After treatment with different concentrations of statins and insulin, the 2-[3H]-DG uptake showed a significant negative correlation with the concentration of atorvastatin (P<0.05), and no significant correlation with pravastatin and rosuvastatin. The mRNA and protein expression levels of GLUT4 and IRs-1 in primary cultured cardiomyocytes were both significantly reduced by atorvastatin treatment (P<0.05). Pravastatin and rosuvastatin showed no significant effects on GLUT4 and IRs-1 expression. The mRNA and protein expression levels of RhoA both showed no significant difference when treated with the 3 statins.

CONCLUSIONS: These results confirm that atorvastatin can inhibit insulin-induced glucose uptake in primary cultured rat cardiomyocytes by regulating the PI3K/Akt insulin signal transduction pathway.

Keywords: Deoxyglucose - pharmacokinetics, Adipocytes - drug effects, Glucose - pharmacokinetics, Glucose Transporter Type 4 - metabolism, Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology, Insulin - pharmacology, Insulin Receptor Substrate Proteins - metabolism, Myocytes, Cardiac - metabolism, Phosphatidylinositol 3-Kinases - metabolism, RNA, Messenger - genetics, Random Allocation, Signal Transduction - drug effects, Tritium