title: Effects of simvastatin on glucose metabolism in mouse MIN6 cells.
abstract: The aim of this study was to investigate the effects of simvastatin on insulin secretion in mouse MIN6 cells and the possible mechanism. MIN6 cells were, respectively, treated with 0  μ M, 2  μ M, 5  μ M, and 10  μ M simvastatin for 48 h. Radio immunoassay was performed to measure the effect of simvastatin on insulin secretion in MIN6 cells. Luciferase method was used to examine the content of ATP in MIN6 cells. Real-time PCR and western blotting were performed to measure the mRNA and protein levels of inward rectifier potassium channel 6.2 (Kir6.2), voltage-dependent calcium channel 1.2 (Cav1.2), and glucose transporter-2 (GLUT2), respectively. ATP-sensitive potassium current and L-type calcium current were recorded by whole-cell patch-clamp technique. The results showed that high concentrations of simvastatin (5  μ M and 10  μ M) significantly reduced the synthesis and secretion of insulin compared to control groups in MIN6 cells (P < 0.05). ATP content in simvastatin-treated cells was lower than in control cells (P < 0.05). Compared with control group, the mRNA and protein expression of Kir6.2 increased with treatment of simvastatin (P < 0.05), and mRNA and protein expression of Cav1.2 and GLUT2 decreased in response to simvastatin (P < 0.05). Moreover, simvastatin increased the ATP-sensitive potassium current and reduced the L-type calcium current. These results suggest that simvastatin inhibits the synthesis and secretion of insulin through a reduction in saccharometabolism in MIN6 cells.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China.
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China.
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China.
authors.forename: Shaopeng
authors.initials: S
authors.lastname: Zhan
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Chaoyang Hospital, Capital Medical University, 8th Gongtinanlu Road, Chaoyang District, Beijing 100020, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China.
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects; D051379:Mice; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000737:chemistry; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D011863:Radioimmunoassay; D060888:Real-Time Polymerase Chain Reaction; D019821:Simvastatin / Q000627:therapeutic use*; D000099161:Kcnj11 Channel
chemical_list: D000255:Adenosine Triphosphate; D001786:Blood Glucose; D020746:Calcium Channels, L-Type; D005947:Glucose; D051273:Glucose Transporter Type 2; D000960:Hypolipidemic Agents; D007328:Insulin; D011188:Potassium; D024661:Potassium Channels, Inwardly Rectifying; D019821:Simvastatin; D000099161:Kcnj11 Channel; C514350:CACNA1C protein, mouse; C495682:Slc2a2 protein, mouse