宫内发育迟缓(IUGR)是导致2型糖尿病(T2DM)的重要因素，但其机制不明确。新近文献报道，长非编码RNA(LncRNA)在IUGR、胰岛功能损伤及糖尿病的发生中起重要作用。本课题组通过RNA测序技术发现TUG1在IUGR小鼠胰岛中的表达显著性下调，且高表达于正常小鼠胰腺组织；在细胞水平，干扰TUG1导致胰岛素的分泌减少及细胞凋亡增加；通过RIP技术证明TUG1可以结合EZH2，RNA测序及生物信息学分析发现Hes1可能为TUG1的下游靶基因。我们提出假说：TUG1可以通过结合EZH2，介导Hes1转录沉默，调控胰岛细胞功能。本课题组通过体内、体外模型、大数据分析、糖耐量实验、RNA干扰、RIP技术、CHIP技术等手段，多角度探讨TUG1在IUGR导致胰岛功能损伤发生中的作用。从TUG1这个新视点为探讨IUGR介导T2DM胰岛功能损伤的发生机制奠定基础。

Many epidemiological studies have linked intrauterine growth retardation (IUGR) to type 2 diabetes mellitus(T2DM) during adult life, but the molecular mechanisms responsible for the changes are not elucidated. Recent studies have shown that long non-coding RNAs (LncRNAs) play important role in IUGR, islet dsfunction and diabetes mellitus. Our previous work showed that the expression of Taurine Upregulated Gene 1(TUG1) was significantly downregulated in the islet of IUGR mice by RNA sequencing and significantly higher in the mice pancreas than in other tissues. Interference of TUG1 could inhibit GSIS function and promote apoptosis of islet beta cell. With RNA immunoprecipitation(RIP)，we found that TUG1 could bind to EZH2. Moreover, we found that Hes1 might be target gene of TUG1 by RNA sequencing and bioinformatics analysis. Thus, it is hypothesized that TUG1 is involved in islet dysfunction and diabetes development in IUGR mice and these effects may be mediated by silencing Hes1 transcription by binding TUG1 to EZH2. Therefore, in this study, we will choose IUGR mice and db/db mice as animal models and use glucose tolerance test, RNA sequencing, real time PCR, Western blot, RIP, chromatin immunoprecipitation(CHIP) et.al to verify the effect of TUG1 on mice islet function in vivo and in vitro and to explore the mechanisms of it furtherly. This work will help to enrich the theory of IUGR induced islet dysfunction and T2DM.