多巴胺对大鼠胰岛素分泌的影响及机制研究  

Effect of DA on insulin secretion from rat pancreatic cells and possible mechanism

作　　者：钟向琴 丁亚琴[1] 任乐乐[1] 白涛[1,2] 刘萌萌[1] 刘云峰[2] 章毅[1] ZHONG Xiang-qin DING Ya-qin REN Le-le BAI Tao LIU Meng-meng LIU Yun-feng ZHANG Yi(Dept of Pharmacology Dept of Endocrinology of the First Hospital, Shanxi Medical University, Taiyuan 030001,China)

机构地区：[1]山西医科大学基础医学院药理学教研室,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》2017年第5期653-656,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81670710;81373464;81273564;81270882);山西省留学回国人员科技活动项目择优资助(No 2016-97);山西省自然科学基金资助项目(No 2013011047-3)

摘　　要：目的研究多巴胺(dopamine,DA)对大鼠胰岛素分泌的影响及可能机制。方法♂SD大鼠的胰腺经过胶原酶P消化、Histopaque 1077梯度离心后得到纯化的胰岛,DispaseⅡ将胰岛消化为单个细胞。应用胰岛素分泌实验来验证DA对胰岛素分泌的作用,通过膜片钳技术和钙成像技术记录β细胞内向性钙电流、动作电位时程和细胞内Ca^(2+)浓度,研究DA对大鼠胰岛素分泌的作用机制。结果在2.8 mmol·L^(-1)的葡萄糖中,DA对胰岛素的分泌没有产生明显的影响;在16.7 mmol·L^(-1)的葡萄糖中,DA呈浓度依赖性抑制胰岛素的分泌。DA干预后,抑制了胰岛β细胞上内向性钙电流,缩短动作电位时程,减少了细胞内Ca^(2+)浓度。结论 DA通过抑制β细胞上内向性钙电流,进而缩短了动作电位的时程,降低细胞内Ca^(2+)浓度,最终抑制胰岛素的分泌。Aim To investigate the effects of dopamine（DA）on insulin secretion from rat islets and the possible mechanism.Methods Pancreatic islets were obtained from the pancreatic of male SD rats by collagenase P digestion and histopaque-1077 density gradient separation.Insulin secretion experiment was used to observe the change of insulin release after DA treatments.As to study the potential mechanisms of the effects of DA, patch-clamp experiment and calcuim image technique were applied to test the depolarization-evoked Ca2＋ currents, action potential duration and intracellular Ca2＋ concentration.Results In 2.8 mmol·L^-1 glucose, DA had no effect on insulin secretion; in 16.7 mmol·L^-1 glucose, dopamine inhibited insulin secretion in a dose-dependent manner.DA inhibited the inward calcium current, shorten the action potential duration, and reduced the intracellular Ca2＋ concentration.Conclusion DA inhibits insulin secretion maybe by decreasing the inward calcium current leading to shorten the action potential duration and reduce the intracellular Ca2＋ concentration.

关 键 词：多巴胺 胰岛Β细胞 胰岛素分泌 电压门控性Ca2+通道 动作电位 钙成像 

分 类 号：R-332[医药卫生] R322.57