The Effect Of Simvastatin On Function Of Mouse Beta-cells And Its Mechanisms

Objective: To observe the influence of simvastatin on insulin secretion function ofmouse pancreatic β-cells MIN6cell line and to explore its possible mechanisms.Methods: The MIN6cells were randomly divided into group NC, group A, group Band group C, and were cultured for48h with0,2,5and10μmol/L concentration ofsimvastatin of15%fetal bovine serum in high glucose DMEM medium respectively.The influence of simvastatin on insulin secretion of MIN6cells was measured byradioimmunoassay. The contents of ATP in MIN6cells were measured by biologicalchemiluminescence method (luciferase method). Real-Time PCR was performed toinspect the mRNA expression levels of Kir6.2, Cav1.2and GLUT2; the proteinexpression levels of Kir6.2, Cav1.2and GLUT2were detected by Western blot.Results: The medium or high concentration of simvastatin(5μmol/L,10μmol/L)markedly decreased the insulin synthesis and secretion of MIN6cells（P＜0.05）;Compared with normal control group,the content of ATP was markedly decreased inMIN6cells of simvastatin groups（all P＜0.05）; Compared with normal controlgroup,the mRNA expression level of Kir6.2was significantly up-regulated in MIN6cells of each treatment group of simvastatin（all P＜0.01）,the mRNA expression levelof Cav1.2was significantly down-regulated in5μmol/L and10μmol/L groups ofsimvastatin（P＜0.01vs control in both groups）, the mRNA expression level ofGLUT2was markedly down-regulated in5μmol/L and10μmol/L groups ofsimvastatin（P＜0.05）; the protein expression of Kir6.2was significantly increased in5μmol/L and10μmol/L groups of simvastatin than in control group（P＜0.01vscontrol in both groups），the protein expression levels of Cav1.2and GLUT2weremarkedly decreased in10μmol/L group of simvastatin than in control group（P＜0.01vs control in both groups）,the protein expression level of Cav1.2was markedly decreased in5μmol/L group compared to control group（P＜0.01）.Conclusions: The simvastatin showed some inhibitory effects on insulin synthesisand secretion produced by mouse pancreatic β-cells MIN6cell line. And it may affectinsulin synthesis and secretion via suppressing ATP level in MIN6cells, upregulatingthe expression of Kir6.2gene and downregulating the expression of Cav1.2andGLUT2genes in MIN6cells. The simvastatin may be involved in pancreatic β-cellsdysfunction in type2diabetes.