近年来，全球糖尿病的发病率持续升高。胰岛素抵抗（IR）是2型糖尿病（T2DM）的重要发病机制，其产生的分子机理尚不明确。长链非编码RNA（lncRNA）作为重要的调控分子，在糖尿病的发病过程中具有不可忽视的作用。我们前期在小型猪模型中初步发现了3个可能与T2DM发病相关的lncRNA。本研究拟构建广西巴马小型猪T2DM模型获得易感与非易感个体，通过肝脏转录组分析筛选易感性相关的候选lncRNA，并在mRNA、蛋白和细胞水平验证lncRNA与其靶基因的相互作用关系，确定影响IR功能的lncRNA。利用CRISPR/Cas9系统构建lncRNA敲除转基因猪T2DM模型，并在模型中进一步验证lncRNA的功能，确定其影响T2DM易感性的作用机制。这将为研究人类糖尿病发生的分子机理及治疗方法提供新的理论依据。

In recent years, the incidence of diabetes in the world is rising continuously. Insulin resistance (IR) is an important pathogenesis of type 2 diabetes mellitus (T2DM). The molecular mechanism of insulin resistance is not clear. Long non-coding RNA (lncRNA), as an important regulator, plays an important role in the pathogenesis of diabetes. Our previous study found 3 lncRNAs associated with T2DM in the mini-pig models. This study intends to construct Guangxi Bama-min pig T2DM models, obtain the susceptible and non-susceptible individuals. Searching susceptibility-related candidate lncRNAs through the liver transcriptome analysis, and validating the interactions with its target genes in mRNA, protein and cell levels, and confirming the lncRNA which effecting of IR function. Then we will build lncRNA-knockout transgenic T2DM pig models using CRISPR/Cas9 system, the function of the lncRNA will be further verified in the model, and the mechanism of its influence on T2DM susceptibility will be determined. These results will provide a new theoretical basis for the study of the molecular mechanism and treatment of human diabetes.