JBC：Neurogenin 3是胰岛细胞发育的关键基因
生物谷报道：在一项发表于5月18 日Journal of Biological Chemistry (JBC)中的研究报告，伦敦帝国理工学院附属医院的研究人员提出了胚胎制造可分泌胰岛素的细胞之关键因素。 这项研究结果有助于发展出治疗糖尿病的新疗法。
研究发现，葡萄糖扮演着重要的角色，使健康的胰岛beta 细胞在胚胎中的胰脏中发育。葡萄糖可促进一种名为Neurogenin 3的基因来启动另一个基因NeuroD，对于beta 细胞的正常发展是相当重要的。如果葡萄糖含量过低，这个基因将不会活化。胰岛素是调控葡萄糖的主要激素，如果beta 细胞无法生产足够的胰岛素，就会导致糖尿病。
研究人员表示，这项研究结果显示了外在因素如葡萄糖，可能会调控分泌胰岛素的细胞之发育方式，所以将有可能扭转糖尿病患者之beta 细胞的缺陷而治疗糖尿病（主要针对I型糖尿病）。
(资料来源 : Bio.com)
英文原文链接：
原始出处:
Glucose Is Necessary for Embryonic Pancreatic Endocrine Cell Differentiation*
Ghislaine Guillemain
1, Gaëlle Filhoulaud2, Gabriela Da Silva-Xavier
3, Guy A. Rutter4, and Raphaël Scharfmann
From the University Paris-Descartes, Faculty of Medicine, INSERM, Necker Hospital, EMI 363 and U845, 75730 Paris cedex 15, France and the Department of Cell Biology, Division of Medicine, Imperial College London, Exhibition Road, SW7 2AZ, United Kingdom
Abstract
Mature pancreatic cells develop during embryonic life from endodermal progenitors, and this developmental process depends on activation of a hierarchy of transcription factors. While information is available on mesodermal signals controlling pancreas development, little is known about environmental factors, such as the levels of nutrients including glucose, that may control this process. Here, we studied the effects of glucose on pancreatic cells development. We used an in vitro model where both endocrine and acinar cells develop from early pancreatic and duodenal homeobox-1 (PDX1)-positive embryonic pancreatic progenitors. We first showed that glucose does not have a major effect on global pancreatic cell proliferation, survival, and acinar cell development. On the other hand, glucose controlled both alpha and beta cell development. Specifically, the surface occupied by insulin-positive cells was 20-fold higher in pancreases cultured in presence than in absence of glucose, and this effect was dose-dependent over the range 0.5-10 mM. Glucose did not appear to control beta cell development by activating the proliferation of early progenitors or beta cells themselves but instead tightly regulated cell differentiation. Thus, glucose did not modify the pattern of expression of Neurogenin3, the earliest marker of endocrine progenitor cells, but was necessary for the expression of the transcription factor NeuroD, a direct target of Neurogenin3 known to be important for proper pancreatic endocrine cell development. We conclude that glucose interferes with the pancreatic endocrine cells development by regulating the transition between Ngn3 and upstream NeuroD.
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