多巴胺及D_1样受体激动剂SKF38393对大鼠胰岛素分泌的影响及机制

Effect of dopamine and D_1-like receptor agonist SKF38393 on insulin secretion in rats and its mechanism

目的研究多巴胺及D_1样受体激动剂SKF38393(SKF)对大鼠胰岛素分泌的影响及其机制。方法雄性Wistar大鼠胰腺中注入胶原酶P,分离胰腺并经11 min消化和梯度离心得到胰岛组织颗粒。分离的胰岛经乙二胺四乙酸(EDTA)络合、分散酶(Dispase)Ⅱ进一步消化得到单个胰岛细胞。胰岛组织经挑选、分组和不同药物干预后,用放射免疫分析法检测胰岛素分泌量的不同。通过全细胞膜片钳技术记录胰岛B细胞电压依赖性钙通道电流,进而深入探究多巴胺对大鼠胰岛素分泌调控的机制。结果在16.7 mmol/L的葡萄糖环境中,多巴胺和D_1样受体激动剂SKF皆呈浓度梯度依赖性的方式抑制胰岛素分泌。胰岛B细胞在给予多巴胺和SKF干预后,均可使细胞上的电压依赖性钙通道电流减少。结论多巴胺及SKF均呈浓度梯度依赖性的方式抑制葡萄糖刺激的胰岛素分泌,这种作用与电压依赖性钙通道和D_1样受体有关;

Objective To investigate the effect of dopamine and D1-like receptor agonist SKF38393（SKF） on insulin secretion in rats and its mechanism.Methods Collagenase P was injected into the pancreas of male Wistar rats. The pancreas was isolated, and the islet tissue granules were obtained by enzyme digestion and gradient centrifu-gation for 11 min. The isolated islets were further conjugated with EDTA and digested with dispase Ⅱ to obtain individual islet cells, and the difference in insulin secretion was measured by radioimmunoassay. The whole-cell patchclamp technique was used to record the voltage dependent calcium channel current of islet B cells, and therebyto fur-ther explore the mechanism of dopamine on regulation of insulin secretion in rats. Results In 16.7 mmol/L glucose condition, the insulin secretion was inhibited by dopamine or D1-like receptor agonist SKF38393 in a concentration gradient-dependent manner. The voltage-dependent calcium channel currents on islet B cells were reduced by given dopamine or SKF intervention. Conclusion Both dopamine and SKF may inhibit glucose-stimulated insulin secretion in a concentration gradient-dependent manner, which is related to voltage-dependent calcium channels and D1-like receptors.