生物谷：根據(jù)發(fā)表在7月10日的刊物Journal of Biological Chemistry上的結(jié)果,，人體制造胰島素的能力或許可以通過抑制一種新發(fā)現(xiàn)的分子而得到提高,，從而幫助治療糖尿病。
這一分子被稱為miR124,，它是一種microRNA分子,，由倫敦帝國學(xué)院和法國INSERM U145及EMI 0363的科學(xué)家共同發(fā)現(xiàn)。研究小組認(rèn)為,，miR124阻礙了胰臟中胰島素的生成,。它通過控制分泌胰島素的β細(xì)胞的多個基因而實現(xiàn)這一點。
胰島素負(fù)責(zé)控制體內(nèi)血糖濃度,，一旦胰島素不足，就會導(dǎo)致糖尿病,。因此科學(xué)家相信,，如果找到抑制miR124或者其它相關(guān)的microRNA的藥物，就可以保證身體產(chǎn)生更多的胰島素,，從而幫助對抗糖尿病,。
DNA通過RNA將基因信息轉(zhuǎn)化為蛋白質(zhì)，而microRNA結(jié)合到特定信使RNA上,，阻止翻譯過程的發(fā)生,。它們阻礙蛋白質(zhì)的合成然后干擾細(xì)胞的正常活動,。某些合成分子可以關(guān)閉microRNA的活動,，因此科學(xué)家希望可以駕馭它們的這一特性來關(guān)閉某些microRNA，包括miR124,。小組同時期望了解,，在編碼miR124的基因中存在的多態(tài)現(xiàn)象是否使得某些人更容易患上糖尿病。
來自倫敦帝國學(xué)院醫(yī)學(xué)系得Guy Rutter教授是此項研究的作者之一,，他表示：“科學(xué)家們僅僅在數(shù)年前才發(fā)現(xiàn)microRNA的重要性,。而發(fā)現(xiàn)這一特定的microRNA在控制胰島素產(chǎn)生過程中起著基本作用是令人興奮的，這將幫助我們找到治療糖尿病的新工具,，目前糖尿病影響著5%的人群,，并且其發(fā)生率正在逐年上升。”此項研究得到了多個研究機(jī)構(gòu)的支持,。（教育部科技發(fā)展中心）
原始出處:
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.
原文鏈接：http://www.physorg.com/news103292873.html
