长链非编码RNA-xist在氧化应激诱导胰岛β细胞功能缺陷及胰岛素信号通路异常中的作用机制

胰岛β细胞功能缺陷导致胰岛素分泌缺乏是2型糖尿病发生的关键环节,氧化应激是导致β细胞功能受损的重要因素。非编码RNA广泛参与人体生理病理活动,与众多疾病密切相关。迄今对非编码RNA与糖尿病的关系仍知之甚少。我们的预实验结果提示长链非编码RNA-xist(lncRNA-xist)是2型糖尿病的易感基因,并与胰岛素信号通路相关基因TCF7L2存在共表达。TCF7L2是维持胰岛β细胞分泌胰岛素的必要条件,但其调控机制有待进一步探讨。为此我们提出假说: lncRNA-xist—TCF7L2可能参与调控氧化应激诱导的β细胞胰岛素信号通路异常,导致胰岛素分泌减少。为验证这一假说,我们将从lncRNA这个新视点,通过MIN6细胞、db/db小鼠模型，采用腺病毒转染、RNA干扰、分子生物学手段探讨lncRNA-xis对胰岛素信号通路的调控,阐明2型糖尿病β细胞功能缺陷的分子机制,为防治糖尿病提供新思路。

Pancreatic β cell dysfunction leading to a lack of insulin secretion is the key part to type 2 diabetes mellitus. Oxidative stress is an important factor of β-cell dysfunction. Non-coding RNA involved in human body pathophysiology is closely related to many diseases. So far, little study has been examined on the relationship between non-coding RNA and diabetes. Our pilot study suggested that long non-coding RNA-xist (lncRNA-xist) is a susceptibility gene of type 2 diabetes mellitus, and co-expression with TCF7L2, a related gene of insulin signaling pathway. TCF7L2 is a necessary for maintaining insulin secretion in islet β cells. However, the mechanisms still needed to be further explored. Therefore, we propose the hypothesis that lncRNA-xist-TCF7L2 may be involved in the regulation of abnormity of insulin signaling pathway induced by oxidative in β cell, resulting in reducing insulin secretion. To test this hypothesis, we will explore the regulation of lncRNA-xist and its target gene TCF7L2 of β cell insulin signaling pathway in MIN6 cells and db/db mice model by using adenovirus vector transfection, RNA interference and molecular biology methods. We will take the new perspective of long non-coding RNA to clarify the molecular mechanism of islet β cell dysfunction in type 2 diabetes and provide new ideas and new methods for the prevention and treatment of diabetes.