ATP调控大鼠胰腺β细胞胰岛素分泌的双重作用

Dual Role of Extracellular ATP on Secretion of Insulin in Rat Pancreatic β Cells

实验以大鼠胰腺β细胞为研究对象,采用荧光测钙和全细胞膜片钳膜电容测量技术,研究ATP对胞内钙离子信号和细胞分泌的影响,并初步探讨了其作用机制.实验表明:胞外ATP刺激通过动员细胞内thapsigargin敏感的钙库Ca2+释放,使大鼠胰腺β细胞内的游离钙离子浓度显著升高,细胞外的ATP信号对β细胞胰岛素分泌有双向调节作用,其一,主要通过降低去极化引起的钙电流而对β细胞胰岛素分泌产生较弱的抑制作用,其二,细胞在静息状态下,ATP通过动员胞内钙库的Ca2+释放使胞浆中的钙离子浓度显著增加,触发β细胞强烈分泌胰岛素.ATP的这种双向调节可能对胰岛素分泌的精确调控具有重要的生理意义.

By measurement of intracellular flee Ca^2＋ concentration using micro-fluorometric assay, whole cell calcium current and capacitance, regulative effects of extracelluar ATP on insulin secretion in primary rat β cells were studied. ATP elevated intracellular flee Ca^2＋ concentration by mobilizing intercellular IP3 sensitive calcium pool, therefore it induced a strong secretion in resting β cells. Meanwhile, ATP attenuated depolarization-evoked Ca^2＋ influx and inhibited secretion induced by excitation of cell. The results demonstrated that ATP had dual regulative effects on insulin secretion in rat β cell. It is suggested extracellular ATP signal maybe have different effects on the two phases of insulin secretion in organisms： a negative feedback effect on the first phase, and a positive feedback effect on the second. Although, there are open questions to be resolved, the data support cue to the further study of mechanism underlying ATP regulation of insulin secretion.