Formation of Pancreatic Islets Involves Coordinated Expansion of Small Islets and Fission of Large Interconnected Islet-like Structures
Formation of Pancreatic Islets Involves Coordinated Expansion of Small Islets and Fission of Large Interconnected Islet-like Structures
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DOI：
10.1016/j.bpj.2011.06.042
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发表时间：
2011-08-03
影响因子：
3.4
通讯作者：
Hara, Manami
中科院分区：
文献类型：
--
作者：
Jo, Junghyo;Kilimnik, German;Hara, Manami
胰岛是维持葡萄糖稳态的微器官，其大小范围从小于 10 个细胞的小簇到由数千个内分泌细胞组成的大胰岛。不同物种之间的胰岛大小分布相似且与体型无关，这表明胰岛大小存在内在限制。关于调节胰岛大小的机制知之甚少。我们对完整小鼠胰腺从出生到八个月的胰岛大小分布变化进行了全面分析，包括量化这一动态生物过程的数学模型。发育过程中胰岛的生长依赖于大小，较小的胰岛优先扩张，而大的相互连接的胰岛样结构的裂变在断奶时约三周龄时最活跃。胰岛形成过程在四周后完成，此后几乎没有或没有新的胰岛形成，并且无论胰岛大小如何，所有β细胞在成体中都具有较低的增殖潜力。同样，在患有胰岛素瘤的小鼠中，包括裂变在内的早期产后发育过程遵循相同的时间过程，而在成年小鼠中没有新的胰岛形成。然而，肿瘤进展导致胰岛生长不受控制，并加速较大胰岛的扩张。因此，胰岛的形成和生长是一个严格调控的过程，涉及小胰岛的优先扩张和大的互连胰岛样结构的裂变。
The islets of Langerhans, micro-organs for maintaining glucose homeostasis, range in size from small clusters of < 10 cells to large islets consisting of several thousand endocrine cells. Islet size distributions among various species are similar and independent of body size, suggesting an intrinsic limit to islet size. Little is known about the mechanisms regulating islet size. We have carried out a comprehensive analysis of changes of islet size distribution in the intact mouse pancreas from birth to eight months, including mathematical modeling to quantify this dynamic biological process. Islet growth was size-dependent during development, with preferential expansion of smaller islets and fission of large interconnected islet-like structures occurring most actively at approximately three weeks of age at the time of weaning. The process of islet formation was complete by four weeks with little or no new islet formation thereafter, and all the beta-cells had low proliferation potential in the adult, regardless of islet size. Similarly, in insulinoma-bearing mice, the early postnatal developmental process including fission followed the same time course with no new islet formation in adults. However, tumor progression led to uncontrolled islet growth with accelerated expansion of larger islets. Thus, islet formation and growth is a tightly regulated process involving preferential expansion of small islets and fission of large interconnected islet-like structures.