胰岛素是机体血糖平衡的重要调控因子，如果胰岛素分泌不足或者发生胰岛素抵抗会引起糖尿病。胰岛素是通过调节型分泌途径从胰岛β细胞中分泌的，此过程是一个受精确调控的胰岛素囊泡分泌的过程。AP蛋白复合体是囊泡转运和蛋白分选过程中的一种重要的调控因子。我们前期的研究发现AP-3可能参与胰岛素囊泡的成熟过程，本项目中我们将利用多种先进的技术方法，从多种角度深入研究AP-3在胰岛β细胞的胰岛素囊泡生成和成熟过程中的功能和分子机制，旨在揭示AP-3在胰岛β细胞中的精确定位，解析AP-3蛋白复合体的结构，阐明AP-3在胰岛素囊泡生成和成熟过程的膜重塑和蛋白分选中的作用机制。因此，本项目是研究一个关键的蛋白分子在一个重要的生物学过程中的作用机制，具有很强的创新性和重要的科学意义。研究结果将揭示AP-3蛋白复合体在胰岛素囊泡分泌和胰岛素释放中扮演的角色，为糖尿病发生发展的分子机制提供新的理论基础和研究方向。

Insulin is a key regulator to maintain glucose homeostasis. Insulin deficiency and insulin resistance are considered as major risk factors in the etiology of type 2 diabetes mellitus. More than 99% of the insulin is secreted from the pancreatic β cells via a regulated secretory pathway. In the secretory pathways, cargo proteins destined for transporting to distinct locations are collectively assembled into vesicles and delivered to their target sites by vesicular trafficking. The AP (adaptor protein) complexes play a critical role in this process. Our preliminary research data demonstrated that AP-3 was involved in the maturation of insulin secretory granule in pancreatic β cells. In this project, we will employ a series of cutting-edge techniques to conduct a thorough research on the functions and molecular mechanisms of AP-3 in the biogenesis and maturation of insulin granule in pancreatic β cells. We will uncover the precise localization of AP-3 in pancreatic β cells, determine the structure of AP-3 complex, and clarify the molecular mechanisms of AP-3 involved in the membrane remodeling and protein sorting in insulin granule biogenesis and maturation process. So this project will reveal novel functions and molecular mechanisms of a key protein complex involved in a crucial biological process. It will uncover novel roles of AP-3 in insulin granule exocytosis and biphasic insulin release, thereby providing new molecular basis and extending new aspect of the etiology of type 2 diabetes mellitus. Thus, this project has enough novelty and important scientific significance.