摘要
目的观察沉默信息调节因子1(SIRT1)对小鼠胰岛B细胞株MIN6胰岛素分泌功能的影响,并初步探讨其机制。方法应用逆转录聚合酶链反应(RT-PCR)法检测SIRT1及其下游肝脏X受体(LXRs)的mRNA在MIN6细胞中的表达,应用酶链免疫吸附测定法(ELISA)分别检测SIRT1激动剂白藜芦醇(resveratrol)和SIRT1抑制剂sirtinol对MIN6细胞胰岛素分泌影响的量效与时效关系及SIRT1下游调控基因LXRs抑制剂22(S)-羟化胆固醇(22-S-HC)对MIN6细胞胰岛素分泌功能的影响。结果 SIRT1激动剂resveratrol能够明显的促进MIN6细胞的胰岛素分泌,SIRT1抑制剂sirtinol则对MIN6细胞的胰岛素分泌具有一定的抑制作用,且均呈一定程度的时间-剂量依赖关系。SIRT1的活性变化不会引起LXRs的mRNA表达变化。SIRT1下游调控因子LXRs的抑制剂22-S-HC能够部分拮抗白藜芦醇对MIN6细胞的胰岛素分泌的促进作用。结论 SIRT1的活性对于MIN6细胞的胰岛素分泌具有明显的正相关调节作用,其机制可能与SIRT1下游的核转录因子LXRs的活性有关。
Objective To study the possible regulation and potential mechanism of SIRT1 deacetylase in insulin secretion in the mouse MIN6 cell line.Methods The mRNA expression levels of SIRT1 and its downstream mediator,LXRs,were detected by RT-PCR.After MIN6 cells were co-incubated in the presence or absence of a SIRT1 activator,resveratrol,a SIRT1 inhibitor,sirtinol,or a LXRs inhibitor,22-S-HC,respectively.The supernatants were collected and the contents of insulin secreted by MIN6 cells were analyzed by ELISA.Results Resveratrol promoted the insulin secretion from MIN6 cells in a dosage-and time-dependent way,while sirtinol suppressed its secretion in a similar manner.The increased insulin secretion induced by resveratrol was significantly attenuated by 22-S-HC,which inhibited LXRs.Conclusion Sirt1 is a positive regulator of insulin secretion in MIN6 cell line,which is mediated by an LXRs-dependent pathway.
出处
《中南药学》
CAS
2010年第5期332-335,共4页
Central South Pharmacy
基金
国家自然科学基金项目(No.30871017)
