Regulation of pancreatic beta-cell electrical activity and insulin release by physiological amino acid concentrations
Regulation of pancreatic beta-cell electrical activity and insulin release by physiological amino acid concentrations
复制标题
DOI：
10.1007/s004240050334
复制
发表时间：
1997-04-01
影响因子：
4.5
通讯作者：
Soria, B
中科院分区：
文献类型：
--
作者：
Bolea, S;Pertusa, JAG;Soria, B
葡萄糖和氨基酸对胰岛素释放的相互促进作用尚不清楚。在本研究中，使用新鲜分离的小鼠胰岛测定了在进食（aa（FD））和禁食（aa（FD））动物中发现的浓度的氨基酸和葡萄糖混合物对电活动和胰岛素释放的影响。与用aa（FT）混合物和单独用葡萄糖（G）（10 mmol/l）灌注的胰岛相比，用aa（FD）混合物灌注的胰岛在较低的葡萄糖浓度（5 mmol/l）下显示出电活动的振荡模式。浓度/响应曲线的时间分数所花费的膜电位在活性阶段在aa（FD）刺激的胰岛被发现显着向左移动，并有一个较小的斜率比葡萄糖刺激的胰岛。胰岛素释放遵循相同的模式。这导致葡萄糖的浓度/响应曲线更接近于“体内”记录的曲线。我们还发现，四种氨基酸（亮氨酸、异亮氨酸、丙氨酸和精氨酸）主要负责观察到的效果，并且由于氨基酸和葡萄糖的组合作用，存在胰岛素释放的非线性增强。这种效应在胰岛素释放的第二阶段更加明显，并且依赖于细胞内Ca 2+。这些研究结果表明，氨基酸占大多数的葡萄糖的浓度/响应曲线的峰值偏移，并在葡萄糖诱导的振荡电活动响应的阈值降低，并在生成的Ca 2+尖峰占触发胰岛素释放在较低的葡萄糖浓度。然而，在高葡萄糖浓度下对胰岛素释放的影响不能仅仅通过葡萄糖诱导的电活动的增加来解释。
The mutual enhancement of insulin release by glucose and amino acids is not clearly understood. In this study, the effects on electrical activity and insulin release of a mixture of amino acids and glucose at concentrations found in fed (aa(FD)) and fasted (aa(FD)) animals were determined using freshly isolated mouse islets. Islets perifused with aa(FD) mixture showed an oscillatory pattern of electrical activity at lower glucose concentrations (5 mmol/l) than in islets perifused with the aa(FT) mixture and with glucose (G) alone (10 mmol/l). The concentration/response curve for the fraction of time spent by the membrane potential in the active phase in aa(FD)-stimulated islets was found to be significantly shifted to the left and had a smaller slope than that for glucose-stimulated islets. Insulin release followed the same pattern. This resulted in a concentration/response curve for glucose that was closer to that recorded ''in vivo''. We have also found that four amino acids (leucine, isoleucine, alanine and arginine) are largely responsible for the observed effects and that there is a non-linear enhancement of insulin release as a consequence of the combined effect of amino acids and glucose. This effect was more pronounced in the second phase of insulin release and was dependent on intracellular Ca2+. These findings indicate that amino acids account for most of the leftward shift in the concentration/response curve for glucose and that a reduction in the threshold for the glucose-induced oscillatory electrical activity response and in the generation of Ca2+ spikes accounts for the triggering of insulin release at lower glucose concentrations. Nevertheless, the effects on insulin release at high glucose concentrations cannot be explained solely by the increase in glucose-induced electrical activity.