Cellular communication and heterogeneity in pancreatic islet insulin secretion dynamics.

Cellular communication and heterogeneity in pancreatic islet insulin secretion dynamics.
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DOI:
10.1016/j.tem.2014.02.005
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发表时间:
2014-08
影响因子:
10.9
通讯作者:
Piston, David W.
Piston, David W.
中科院分区:
医学1区
文献类型:
--
作者:
Benninger, Richard K. P.;Piston, David W.

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电活动和胰岛素分泌的协调脉冲是胰岛的标志。当β-细胞解离时,这些协调行为丧失,这也导致在低葡萄糖下胰岛素分泌增加。没有间隙连接的胰岛表现出与分散细胞相似的异步电活动,但它们在低葡萄糖下的分泌仍然被钳制,由阿托他克林机制抑制。缺乏β细胞间隙连接的小鼠具有接近正常的平均胰岛素水平,但由于第一时相和脉冲式胰岛素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。我们回顾了胰岛同步的定量数据和目前已经开发的数学模型来解释这些行为,并产生更好的理解的潜在机制。
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. Islets without gap junctions exhibit asynchronous electrical activity similar to dispersed cells, but their secretion at low glucose 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. 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.
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