Beta-cell development and turnover during prenatal life in humans.
Beta-cell development and turnover during prenatal life in humans.
复制标题
人类产前生命期间 β 细胞的发育和更新。
DOI：
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发表时间：
2010
影响因子：
5.8
通讯作者：
H. Fritsch
中科院分区：
文献类型：
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作者：
J. Meier;Christina U. Köhler;Bacel Alkhatib;C. Sergi;T. Junker;H. Klein;W. Schmidt;H. Fritsch
引言
β细胞再生是未来糖尿病治疗的一个积极研究领域，但人们对人类产前β细胞发育的模式和动态知之甚少。特别是，发育中的胰腺中的β细胞团的数量变化还没有被详细阐明。我们在产前人类中解决了以下问题：i)β细胞发生和胰岛生长的时间是什么？Ii)β细胞复制和凋亡的动态是什么？
方法
胰腺组织取自65个胎龄在妊娠8周之间的人胚胎和胎儿(P.C.)和出生。切片进行胰岛素、胰升糖素、Ki67(增殖标记物)、TUNEL(凋亡标记物)和CD31(血管标记物)染色，并进行形态计量学分析。
结果
胰岛β细胞面积在出生前呈线性增加(r=0.6，P<；0.001)。第一批内分泌细胞位于原始导管上皮内或邻近原始导管上皮内。在第9周开始的新形成的胰岛中，很容易检测到β细胞的复制。(平均频率2.8+/-0.4%)。在胎儿早期，有一小部分细胞共表达胰岛素和胰升糖素。在出生前胰腺发育的所有阶段，内分泌岛和血管的发育之间存在着密切的关系，提示两种细胞类型之间可能存在相互作用。在所有年龄段中，β细胞凋亡率相对较高(1.5+/-0.3%)。
结论
人类的β细胞分化始于公元前9周。往前走。第一内分泌细胞与导管上皮关系密切，提示与前体细胞分化。β细胞的高复制率表明，这一机制在β细胞团的产前扩张中起着重要作用。
INTRODUCTION
beta-cell regeneration is an area under active investigation for the future treatment of diabetes, but little is known about the patterns and dynamics of prenatal beta-cell development in humans. In particular, the quantitative changes in beta-cell mass in the developing pancreas have not been elucidated in detail. We addressed the following questions in prenatal humans: i) what is the timing of beta-cell occurrence and islet growth? ii) What are the dynamics of beta-cell replication and apoptosis?
METHODS
Pancreatic tissue was obtained from 65 human embryos and foetuses aged between 8 weeks post conception (p.c.) and birth. Sections were stained for insulin, glucagon, Ki67 (proliferation marker), TUNEL (apoptosis marker) and CD31 (blood vessel marker), and morphometric analyses were performed.
RESULTS
beta-cells were detected from gestational week 9 onward, whereas glucagon expression was detected already at week 8. The fractional beta-cell area of the pancreas increased in a linear fashion until birth (r=0.60, P<0.001). The first endocrine cells were found within or adjacent to the primitive ductal epithelium. beta-cell replication was readily detected in the newly forming islets already starting at week 9 p.c. (average frequency 2.8+/-0.4%). A small percentage of cells co-expressed insulin and glucagon during the early foetal period. There was a close relationship between the development of endocrine islets and blood vessels during all stages of prenatal pancreas development suggesting a possible interaction between both cell types. The frequency of beta-cell apoptosis was relatively high throughout all ages (1.5+/-0.3%).
CONCLUSIONS
beta-cell differentiation in humans occurs from week 9 p.c. onward. The first endocrine cells are closely associated with the ductal epithelium suggesting differentiation from precursor cells. High rates of beta-cell replication suggest that this mechanism plays an important role in the prenatal expansion of beta-cell mass.
影响因子：
8.2
作者：
Meier, JJ;Bhushan, A;Butler, PC
通讯作者：
Butler, PC