FGF作为重要的功能蛋白家族，其18个成员按结构和功能分为5个旁分泌和1个内分泌亚家族，长期认为旁分泌FGF功能主要为促细胞增殖和组织再生。但最新的研究报道以及申请人在前一个国自然支持下，研究发现旁分泌FGF1具有重要降糖功能，且FGF1引起的FGFR1c受体二聚化程度是控制其双重功能发挥的关键因素。基于此，本课题提出并拟解决两个问题：1）FGF1双重功能特征是否普遍存在于旁分泌FGF家族；2）旁分泌FGF发挥急慢性降糖的作用机制。针对问题1），本课题拟对旁分泌全家族进行筛选以获取代谢调控旁分泌FGFs成员谱并深入揭示该类FGFs共性特征；针对问题2），基于前期组织分布及功能特征分析，本课题重点聚焦肝脏靶点，拟从糖原合成和糖异生角度阐明其发挥急慢性降糖的作用机制。通过本课题实施，不仅可获取旁分泌FGF产生代谢调控功能共性特征，且为日益严峻的糖尿病治疗新靶点和新药物发现提供理论指引。

Fibroblast growth factor (FGF) is an important functional protein family. According to the structure and function, its 18 members are divided into 5 paracrine and 1 endocrine subfamily. For long time, the main function of paracrine FGF was considered for cell proliferation and tissue regeneration. However, the latest research and our study which was supported by NSFC, reported that paracrine FGF1 also has an important hypoglycemic function. Additionally, we demonstrated that the mitogenic and the metabolic activity of FGF1 can be uncoupled by surgically dampening FGF1-FGFR1c dimer stability. This enlightens us to propose two issues: 1) whether the dual functional features of FGF1 are prevalent in all paracrine FGF family members; and 2) how paracrine FGF exerts excellent acute and chronic hypoglycemic functions. For the first question, we plan to screen all paracrine family members to obtain the paracrine FGFs with metabolic regulation, and further reveal their common characteristics. For the second question, based on the previous analysis of tissue distribution and functional characteristics, we will focus on liver targets and intend to elucidate its mechanism of acute and chronic hypoglycemic effects from the aspects of glycogen synthesis and gluconeogenesis. Through this study, we can not only acquire the common features of paracrine FGFs with metabolic function, but also provide theoretical guides for the discovery of the new targets and drugs for the treatment of diabetes.