pdx-1 function is specifically required in embryonic cells to generate appropriate numbers of endocrine cell types and maintain glucose homeostasis
pdx-1 function is specifically required in embryonic cells to generate appropriate numbers of endocrine cell types and maintain glucose homeostasis
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DOI：
10.1016/j.ydbio.2007.10.038
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发表时间：
2008-02-15
影响因子：
2.7
通讯作者：
Wright, Christopher V. E.
中科院分区：
文献类型：
--
作者：
Gannon, Maureen;Ables, Elizabeth Tweedie;Wright, Christopher V. E.
pdy 1基因对于人类和小鼠的胰腺器官形成是必不可少的; pdx 1突变已经在人类糖尿病患者中被鉴定。pdy 1在成人β细胞中的特异性失活揭示了该基因是维持成熟β细胞功能所必需的。在接下来的研究中，Cre-lox策略被用于在胰岛形成之前从妊娠后期开始特异性地从胚胎β细胞中去除pdx 1功能。在胚胎发育过程中胰岛素分泌细胞中pdv 1缺失的动物，出生时血糖水平升高，断奶时明显患有糖尿病。新生儿和成人突变胰岛显示胰岛素（+）细胞数量显著减少，胰高血糖素（+）和生长抑素（+）细胞数量增加。谱系追踪显示，过量的胰高血糖素（+）和生长抑素（+）细胞并不是通过内分泌细胞类型的相互转换而产生的。突变胰岛的检查显示，出生前产生胰岛素的细胞增殖减少，同时产生胰高血糖素的细胞增殖增加。我们认为pdx 1是妊娠晚期产生的13种细胞的增殖和功能所必需的，正常细胞的一个功能是抑制其他胰岛细胞类型的增殖，从而产生适当数量的不同内分泌细胞类型。(c)2007爱思唯尔公司All rights reserved.
The pdy1 gene is essential for pancreatic organogenesis in humans and mice; pdx1 mutations have been identified in human diabetic patients. Specific inactivation of pdy1 in adult beta cells revealed that this gene is required for maintenance of mature beta cell function. In the following study, a Cre-lox strategy was used to remove pdx1 function specifically from embryonic beta cells beginning at late-gestation, prior to islet formation. Animals in which pdv1 is lost in insulin-producing cells during embryogenesis had elevated blood glucose levels at birth and were overtly diabetic by weaning. Neonatal and adult mutant islets showed a dramatic reduction in the number of insulin(+) cells and an increase in both glucagon(+) and somatostatin(+) cells. Lineage tracing revealed that excess glucagon(+) and somatostatin(+) cells did not arise by interconversion of endocrine cell types. Examination of mutant islets revealed a decrease in proliferation of insulin-producing cells just before birth and a concomitant increase in proliferation of glucagon-producing cells. We propose that pdx1 is required for proliferation and function of the 13 cells generated at late gestation, and that one function of normal cells is to inhibit the proliferation of other islet cell types, resulting in the appropriate numbers of the different endocrine cell types. (c) 2007 Elsevier Inc. All rights reserved.