Benninger Richard K P, Piston David W
Department of Bioengineering and Barbara Davis Center, University of Colorado Anschutz Medical campus, Aurora, CO, USA.
Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN, USA.
Trends Endocrinol Metab. 2014 Aug;25(8):399-406. doi: 10.1016/j.tem.2014.02.005. Epub 2014 Mar 26.
Coordinated pulses of electrical activity and insulin secretion are a hallmark of the islet of Langerhans. These coordinated behaviors are lost when β cells are dissociated, which also leads to increased insulin secretion at low glucose levels. Islets without gap junctions exhibit asynchronous electrical activity similar to dispersed cells, but their secretion at low glucose levels is still clamped off, putatively by a juxtacrine mechanism. Mice lacking β cell gap junctions have near-normal average insulin levels, but are glucose intolerant due to reduced first-phase and pulsatile insulin secretion, illustrating the importance of temporal dynamics. Here, we review the quantitative data on islet synchronization and the current mathematical models that have been developed to explain these behaviors and generate greater understanding of the underlying mechanisms.
电活动和胰岛素分泌的协调脉冲是胰岛的一个标志。当β细胞解离时,这些协调行为就会丧失,这也会导致在低葡萄糖水平时胰岛素分泌增加。没有缝隙连接的胰岛表现出与分散细胞相似的异步电活动,但它们在低葡萄糖水平时的分泌仍然被阻断,推测是通过旁分泌机制。缺乏β细胞缝隙连接的小鼠平均胰岛素水平接近正常,但由于第一阶段胰岛素分泌减少和胰岛素脉冲分泌减少而出现葡萄糖不耐受,这说明了时间动态的重要性。在这里,我们回顾了关于胰岛同步化的定量数据以及为解释这些行为并更深入理解潜在机制而开发的当前数学模型。