The Effect Of Simvastatin On The Glucose Metabolism Of Hepatocyte And Its Mechanisms

Objective： To observe the influence of simvastatin on the glucosemetabolism of huaman Hepatoma G2cell line and to explore its possiblemechanisms.Method: We divide the HepG2cells into group NC, group A, group B and groupC randomly, and the cells were cultured for48h in complete mediumWhich contains10nmol/l insulin and0,2,5,10μmol/L concentration ofsimvastatin respectively.The influence of simvastatin on cell viabilityof HepG2cells was measured by MTS assay. The HepG2cells’glucoseconsumption was measured by glucose oxidase method. Real-Time PCR wasperformed to inspect the mRNA expression levels of IR-β,AKT and GLUT2;theprotein expression levels of IR-β,p-AKT and GLUT2were detected byWestern blot.Results：1.When compared with group NC，each treatment concentration ofsimvastatin had no effet on the cell viability of HepG2cells(allP>0.05);2.Compared with group NC，the glucose consumption was markedlydecreased in HepG2cells of simvastatin groups(all P<0.05),and the degreeof reduction depended on the concentration of simvastatin;3. The resultof RT-PCR and western blot showed that the expression level of IR-βand p-AKT was down-regulated significantly in the treatment group ofsimvastatin，and the down-regulated level was more significantly in themedium or high concentration of simvastatin;4.The RT-PCR and western blotshowed that simvastatin had no effet on the expression level of GLUT-2in HepG2cells(all P>0.05).Conclusion：1.Simvastatin showed some inhibitory effects on glycometabolism of hepatocyte.2.Simvastatin may lead to insulinresistance of hepatocyte via downregulating the expression of IR-β andp-AKT in hepatocyte.3.The mechanism of simvastatin result in insulinresistance of hepatocyte may be one of the mechanisms of how statins leadto diabetes mellitus.