生物谷：根据发表在7月10日的刊物Journal of Biological Chemistry上的结果，人体制造胰岛素的能力或许可以通过抑制一种新发现的分子而得到提高，从而帮助治疗糖尿病。
这一分子被称为miR124，它是一种microRNA分子，由伦敦帝国学院和法国INSERM U145及EMI 0363的科学家共同发现。研究小组认为，miR124阻碍了胰脏中胰岛素的生成。它通过控制分泌胰岛素的β细胞的多个基因而实现这一点。
胰岛素负责控制体内血糖浓度，一旦胰岛素不足，就会导致糖尿病。因此科学家相信，如果找到抑制miR124或者其它相关的microRNA的药物，就可以保证身体产生更多的胰岛素，从而帮助对抗糖尿病。
DNA通过RNA将基因信息转化为蛋白质，而microRNA结合到特定信使RNA上，阻止翻译过程的发生。它们阻碍蛋白质的合成然后干扰细胞的正常活动。某些合成分子可以关闭microRNA的活动，因此科学家希望可以驾驭它们的这一特性来关闭某些microRNA，包括miR124。小组同时期望了解，在编码miR124的基因中存在的多态现象是否使得某些人更容易患上糖尿病。
来自伦敦帝国学院医学系得Guy Rutter教授是此项研究的作者之一，他表示：“科学家们仅仅在数年前才发现microRNA的重要性。而发现这一特定的microRNA在控制胰岛素产生过程中起着基本作用是令人兴奋的，这将帮助我们找到治疗糖尿病的新工具，目前糖尿病影响着5%的人群，并且其发生率正在逐年上升。”此项研究得到了多个研究机构的支持。（教育部科技发展中心）
原始出处:
Originally published In Press as doi:10.1074/jbc.M611841200 on April 26, 2007
J. Biol. Chem., Vol. 282, Issue 27, 19575-19588, July 6, 2007
MicroRNA-124a Regulates Foxa2 Expression and Intracellular Signaling in Pancreatic -Cell Lines*
Nadine Baroukh1, Magalie A. Ravier, Merewyn K. Loder, Elaine V. Hill, Ali Bounacer¶, Raphaël Scharfmann¶, Guy A. Rutter, and Emmanuel Van Obberghen2
From the INSERM, U145, Nice, F-06107 France and Université de Nice-Sophia Antipolis, FacultédeMédecine, Institut de Génétique et Signalisation Moléculaire (IFR50), Nice, F-06107 France, the Department of Cell Biology, Division of Medicine, Faculty of Medicine, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom, and the ¶INSERM EMI 0363, Paris F-75015 France and Site Necker, FacultédeMédecine René Descartes, Université Paris-Descartes, Paris, France
MicroRNAs (miRNAs) are short non-coding RNAs that have been implicated in fine-tuning gene regulation, although the precise roles of many are still unknown. Pancreatic development is characterized by the complex sequential expression of a gamut of transcription factors. We have performed miRNA expression profiling at two key stages of mouse embryonic pancreas development, e14.5 and e18.5. miR-124a2 expression was strikingly increased at e18.5 compared with e14.5, suggesting a possible role in differentiated -cells. Among the potential miR-124a gene targets identified by biocomputation, Foxa2 is known to play a role in -cell differentiation. To evaluate the impact of miR-124a2 on gene expression, we overexpressed or down-regulated miR-124a2 in MIN6 -cells. As predicted, miR-124a2 regulated Foxa2 gene expression, and that of its downstream target, pancreatic duodenum homeobox-1 (Pdx-1). Foxa2 has been described as a master regulator of pancreatic development and also of genes involved in glucose metabolism and insulin secretion, including the ATP-sensitive K+ (KATP) channel subunits, Kir6.2 and Sur-1. Correspondingly, miR-124a2 overexpression decreased, and anti-miR-124a2 increased Kir6.2 and Sur-1 mRNA levels. Moreover, miR-124a2 modified basal and glucose- or KCl-stimulated intracellular free Ca2+ concentrations in single MIN6 and INS-1 (832/13) -cells, without affecting the secretion of insulin or co-transfected human growth hormone, consistent with an altered sensitivity of the -cell exocytotic machinery to Ca2+. In conclusion, whereas the precise role of microRNA-124a2 in pancreatic development remains to be deciphered, we identify it as a regulator of a key transcriptional protein network in -cells responsible for modulating intracellular signaling.
原文链接：http://www.physorg.com/news103292873.html
