血管紧张素Ⅱ对离体人胰岛细胞内游离Ca^(2+)及cAMP的影响

Effects of angiotensin Ⅱ on intracellular free calcium and cAMP concentration in human islet β cells

目的探讨血管紧张素Ⅱ对离体人胰岛细胞内游离Ca2+及cAMP的影响,通过体外实验了解血管紧张素Ⅱ影响胰岛细胞分泌功能的相关分子机制。方法以血管紧张素Ⅱ作用于分离纯化的人胰岛细胞,检测细胞内游离Ca2+及cAMP的波动情况,以胰岛灌流实验,绘制胰岛素动态分泌曲线。结果血管紧张素Ⅱ对胰岛β细胞分泌功能的影响呈先升后降双向性,血管紧张素Ⅱ使细胞内游离Ca2+浓度升高,细胞内cAMP的浓度随着血管紧张素Ⅱ浓度的升高而下降。以上作用可被血管紧张素Ⅱ受体阻滞剂Losartan所逆转。结论血管紧张素Ⅱ通过与胰岛β细胞表面血管紧张素Ⅱ受体结合,导致细胞内游离Ca2+及cAMP变化,从而影响胰岛素分泌。

Objective To investigate the effects of angiotensin Ⅱ on intracellular free calcium and cAMP concentration in human islet β cells and to elucidate their role in regulating insulin secretion. Methods The changes in intracellular calcium were measured by confocal laser scanning microscopy using Flou3 - AM - loaded human islet cells. EIA were used to measure changes in intraellular cAMP. Dynamic insulin secretory response was determined by RIA following perfusion of human islets. Results Exposure of the isolated islets to angiotensin Ⅱ induced glucose - stimulated insulin release coupled with increase in intracellular calcium early phase but decrease in late phase. Intracellular cAMP concentration can also be affected by angiotensin Ⅱ. Conclusion The possible mechanisms underlying the angiotensin Ⅱ -induced change of glucose -induced insulin secretion are associated with Ca^2＋ and cAMP signaling pathways.