Formation of a Human β-Cell Population within Pancreatic Islets Is Set Early in Life
Formation of a Human β-Cell Population within Pancreatic Islets Is Set Early in Life
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DOI：
10.1210/jc.2012-1206
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发表时间：
2012-09-01
影响因子：
5.8
通讯作者：
Rhodes, Christopher J.
中科院分区：
文献类型：
--
作者：
Gregg, Brigid E.;Moore, Patrick C.;Rhodes, Christopher J.
背景：胰岛素抵抗可以通过增加功能性胰腺β细胞群来补偿;否则，糖尿病会加重。这种补偿不仅取决于环境和遗传因素，但也对基线β-细胞的质量从其expansion origin.Objective：鲜为人知的是，在人类的基线β-细胞质量的组装。在这里，我们研究了β-细胞群体的形成相对于其他胰岛细胞类型和相关的神经元在整个正常的人类lifes.Design和方法：人胰腺切片来自正常尸体年龄24周过早到72岁进行了免疫荧光检查。胰岛素、胰高血糖素和生长抑素分别用作β细胞、α细胞和δ细胞的标记物。细胞角蛋白-19标记导管细胞，Ki 67细胞增殖，Tuj 1（神经元III类β-微管蛋白）标记neurons.Results：大多数β-细胞新生观察到早产与爆发的β-细胞增殖峰值内的第一个2年的生活。此后，几乎没有观察到β细胞生长的迹象。出生后的α-和δ-细胞的增殖是很少看到的，但导管细胞增殖的浪潮被发现主要与外分泌细胞扩张。β-细胞与α-细胞的比例在幼年时加倍，反映了β-细胞的生长增加，但在儿童时期，β-细胞与δ-细胞的比例变化了7倍，反映了δ-细胞的额外损失。神经元与胰岛的密切联系在发育过程中被注意到，并在整个成年期被保留。可忽略不计的神经元协会外分泌pancreat.Conclusion：人类基线β细胞群体和适当的协会与其他胰岛细胞类型是建立在5岁之前。（J Clin Endocrinol Metab 97：3197-3206，2012）
Context: Insulin resistance can be compensated by increased functional pancreatic beta-cell mass; otherwise, diabetes ensues. Such compensation depends not only on environmental and genetic factors but also on the baseline beta-cell mass from which the expansion originates.Objective: Little is known about assembly of a baseline beta-cell mass in humans. Here, we examined formation of beta-cell populations relative to other pancreatic islet cell types and associated neurons throughout the normal human lifespan.Design and Methods: Human pancreatic sections derived from normal cadavers aged 24 wk premature to 72 yr were examined by immunofluorescence. Insulin, glucagon, and somatostatin were used as markers for beta-, alpha-, and delta-cells, respectively. Cytokeratin-19 marked ductal cells, Ki67 cell proliferation, and Tuj1 (neuronal class III beta-tubulin) marked neurons.Results: Most beta-cell neogenesis was observed preterm with a burst of beta-cell proliferation peaking within the first 2 yr of life. Thereafter, little indication of beta-cell growth was observed. Postnatal proliferation of alpha- and delta-cells was rarely seen, but a wave of ductal cell proliferation was found mostly associated with exocrine cell expansion. The beta-cell to alpha-cell ratio doubled neonatally, reflecting increased growth of beta-cells, but during childhood, there was a 7-fold change in the beta-cell to delta-cell ratio, reflecting an additional loss of delta-cells. A close association of neurons to pancreatic islets was noted developmentally and retained throughout adulthood. Negligible neuronal association to exocrine pancreas was observed.Conclusion: Human baseline beta-cell population and appropriate association with other islet cell types is established before 5 yr of age. (J Clin Endocrinol Metab 97: 3197-3206, 2012)