任乐乐 白涛 刘萌萌

[摘要] 目的 研究多巴胺（dopamine，DA）及其D2样受体对大鼠胰岛素分泌的影响及机制。 方法 向雄性Wistar大鼠的胆总管中注入胶原酶P消化胰腺得到胰岛组织。将胰岛组织在5 g/L的Dispase Ⅱ中消化5 min得到胰岛细胞。根据方法不同以及加入的物质不同，将胰岛组织或胰岛细胞分成对照组、2.8 G、16.7 G、多巴胺组、喹吡罗组、SKF38393组、多巴胺和喹吡罗混合液组。应用放射免疫分析法测定各组胰岛组织分泌的胰岛素含量变化；应用全细胞膜片钳技术测定各组胰岛细胞电压依赖性钾通道的电流变化；应用钙成像技术测定各组胰岛细胞内钙离子浓度的改变。 结果 多巴胺可抑制葡萄糖刺激的胰岛素分泌，该作用与D2样受体的激活有关。多巴胺可能是通过D2样受体，使KV通道激活，缩短动作电位时程，限制Ca2+进入，进而导致了胰岛素分泌的抑制。 结论 多巴胺通过D2样受体增加KV通道电流、降低细胞内Ca2+浓度，从而产生葡萄糖刺激的胰岛素分泌抑制作用。

[关键词] 多巴胺；胰岛素分泌；电压依赖性钾通道；全细胞膜片钳；钙成像

[中图分类号] R322.5 [文献标识码] A [文章编号] 1673-9701（2018）25-0030-05

[Abstract] Objective To study the effect and mechanism of dopamine（DA） and its D2-like receptors on insulin secretion in rats. Methods Collagenase P was injected into the common bile duct of male Wistar rats to obtain the pancreatic islet tissues. Islet cells were obtained by digesting the pancreatic islet tissues in 5 g/L Dispase II for 5 min. According to different methods and substances added， the islet tissues or islet cells were divided into control group， 2.8 G group， 16.7 G group， dopamine group， quinpirole group， SKF38393 group， dopamine group and quinpirole mixture group. Radioimmunoassay was used to determine the changes of insulin secretion in pancreatic islets. The whole-cell patch clamp technique was used to determine the voltage-dependent potassium currents in the islet cells of each group. Calcium imaging technique was used to determine the changes of intracellular calcium concentration in islets of each group. Results Dopamine inhibits glucose-stimulated insulin secretion. This effect is related to the activation of D2-like receptors. Dopamine may activate KV channels through D2-like receptors， shorten the action potential duration and limit Ca2+ entry， which in turn leads to inhibition of insulin secretion. Conclusion Dopamine increases KV channel current and decreases intracellular Ca2+ concentration through D2-like receptors， thereby producing glucose-stimulated insulin secretion inhibition.

[Key words] Dopamine； Insulin secretion； Voltage-dependent potassium currents； Whole-cell patch clamp； Calcium imaging

多巴胺作為一种神经递质，在神经和精神疾病，如精神分裂症、帕金森氏症[1]和药物成瘾等方面起着关键作用[2]。不仅如此，多巴胺对外周神经元作用后的葡萄糖和脂质代谢也尤为重要。其中，多巴胺对胰岛素分泌的影响，特别是对胰腺β细胞功能的影响研究不足。多巴胺通过激活多巴胺受体（DRs）而产生各种生物学效应。DRs属于G蛋白偶联受体家族，根据其生化和药理性质不同，将其分成五种不同的DRs亚型（D1R-D5R）和D1样（D1R、D5R）和D2样（D2R、D3R、D4R）两种亚家族[3]。……