Efaroxan对胰岛素分泌的调控机制研究  

Effects of efaroxan on insulin release from pancreatic β cells

作　　者：章毅[1] 刘云峰[2] 高璟英[1] 丁亚琴[1] 

机构地区：[1]山西医科大学药理学教研室,山西太原030001 [2]山西医科大学第一医院内分泌科,山西太原030001

出　　处：《中国药理学通报》2015年第4期524-527,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81070662;81273564;81373464);山西省自然科学基金资助项目(No2012011039-8;2013011047-3);山西省高等学校优秀青年学术带头人支持计划(No 2011-24);山西省留学人员科技活动项目择优资助;山西省回国留学人员科研资助项目(No 2012-046;2013-111);山西省卫生厅科研课题(No 201201062);中华医学会临床医学科研专项资金项目(No 13040440429);人力资源和社会保障部择优启动项目(No 2013-277)

摘　　要：目的观察Efaroxan的促胰岛素分泌作用特点,并探讨其相关作用机制。方法应用放免法测定不同条件下Efaroxan对大鼠胰岛素分泌的影响。c AMP放射免疫试剂盒测定胰岛细胞内c AMP含量。结果 Efaroxan促进胰岛素分泌作用具有葡萄糖浓度依赖性,其特点是在高浓度葡萄糖条件下(8.3、11.1 mmol·L-1)增强胰岛素分泌,而在低浓度葡萄糖条件下(0、2.8 mmol·L-1)则没有作用。Efaroxan的拮抗剂KU14R可明显抑制Efaroxan对胰岛素分泌的促进作用,并明显的抑制了forskolin和IBMX对胰岛素分泌的促进作用。胰岛c AMP含量检测发现,forskolin和IBMX明显增加了胰岛细胞c AMP含量,但是Efaroxan和KU14R对胰岛c AMP含量没有影响。结论 Efaroxan促进胰岛素分泌作用与激动c AMP下游信号通路有关,KU14R通过阻断c AMP下游信号转导通路发挥抑制Efaroxan、forskolin和IBMX的促胰岛素分泌作用。Aim To study the insulinotropic effects of Efaroxan and the underlying mechanism in rat β cells.Methods Pancreatic islets were isolated by collegenase p digestion. Radioimmunoassay was used to measure insulin secretion and c AMP level in rat pancreatic islets. Results Efaroxan only potentiated insulin secretion at high glucose concentrations（ 8. 3,11. 1 mmol·L^- 1） but not at low glucose concentrations. KU14 R,an antagonist of Efaroxan,remarkably inhibited Efaroxan-potentiated insulin secretion; and similarly,KU14 R significantly inhibited forskolin-induced and IBMX-induced insulin secretion. c AMP measurement showed that forskolin and IBMX significantly increased c AMP levels,but Efaroxan and KU14 R had no effects on c AMP content in pancreatic islets. Conclusion Themechanism of Efaroxan-potentiated insulin secretion is related to downstream of c AMP signaling pathway,KU14 R antagonized the downstream of c AMP signaling leading to its inhibitory effects on Efaroxan,forskolin and IBMX-induced insulin secretion.

关 键 词：EFAROXAN 胰岛素 环磷酸腺苷 KU14R 信号转导 胰岛功能 

分 类 号：R332[医药卫生—人体生理学] R322.57[医药卫生—基础医学]