目前大部分miRNA的功能和机制还不清楚，胰腺miRNA的功能更是知之甚少。我们前期研究结果显示miR-26a调控肝脏代谢，同时又能促进胰腺发育和分化。目前，成年胰腺miR-26a的功能没有研究报道。本项目在大量前期工作基础上，利用我们已有的和正在构建的miR-26a基因工程小鼠，揭示成年β细胞miR-26a的基因表达调控网络及其在II型糖尿病中的功能和分子机制。首先将在多种肥胖和糖尿病小鼠模型中，明确miR-26a与糖尿病的相关性。然后利用β细胞特异性过表达和敲除miR-26a小鼠，确立miR-26a在糖尿病中的功能。并且通过全基因组鉴定β细胞miR-26a的靶基因谱，以β细胞功能和质量为主要线索，构建基因表达调控网络，揭示分子机理。本研究将系统阐明β细胞miR-26a在糖尿病中的功能及其分子机制，可为糖尿病的预防和治疗提供新靶点和新思路，具有非常重要的理论意义和临床转化前景。

miRNAs play critical roles in gene regulation and human diseases. However, the functions and underlying mechanisms of most of miRNAs remain unclear. Pancreas has a central role in diabetes, but the involvement of pancreatic miRNA in this disease is poorly understood. Our previous studies have shown that miR-26a is an important regulator of liver metabolism and is implicated in the development of diabetes. We have also shown that miR-26a is crucial for pancreas development and differentiation. These findings, together with our pilot observations, lead to the hypothesis that miR-26a may regulate pancreatic β cell mass and insulin secretion, thereby contributing to the development of diabetes. To test this hypothesis, the following investigations will be performed. Firstly, we will examine the expression of miR-26a in various obese and diabetic mouse model to establish the link between miR-26a and diabetes. Secondly, by using β cell-specific overexpression or knockout miR-26a mouse models, we will confirm the function of miR-26a in diabetes. Thirdly, the genome-wide interacting map between miR-26a and its targets will be defined in pancreatic islets by using RNA deep seqencing. Finally, we will explore the potential role of miR-26a in autophagy and endoplasmic reticulum stress, which are involved in pancreatic β cell mass and insulin secretion. In summary, this project will establish a novel link between miR-26a, pancreatic β cell function and diabetes, which could provide novel opportunities for treating this disease.