近年来，糖尿病已成为我国重要的公共卫生问题。申请人团队通过在代谢性疾病模型中进行组学筛选与功能验证，创新性发现一个全新的内分泌因子PRDC。目前人们对PRDC的生物学功能及其在疾病中的作用所知甚少，尤其在能量和代谢方面尚无涉及。我们的初步研究发现了令人兴奋的结果：PRDC转基因小鼠糖耐量及胰岛素耐量明显改善，PRDC脂肪组织特异性敲除小鼠血糖水平明显升高，提示其可能参与机体胰岛素敏感性及血糖代谢调控。本课题将在前期研究基础上，进一步利用基因修饰小鼠模型并结合现代分子生物学和细胞生物学研究方法，通过体外和体内功能实验首次创新性分析PRDC对胰岛素敏感性和血糖代谢的调控作用，继而深入探讨PRDC是否通过抑制BMP信号通路影响胰岛素敏感性及其潜在分子机制，并在已建立的人群队列和人群干预研究中进行验证分析，为深入探讨糖尿病发病机制及发现新型药物靶点提供科学数据。

Diabetes has recently become one of serious public health problems in China. Insulin resistance plays a key role in pathophysiological changes of diabetes. Our research group has identified a new endocrine factor PRDC (protein related to DAN and cerberus), whose biological function and role in human disease have remained largely obscure. Little is known about its relationship with energy balance and glucose homeostasis. Fortunately, we have found some exciting results in our previous work on PRDC. Compared with wide type mice, PRDC transgenic mice have significantly improved glucose tolerance and adipose-specific PRDC knockout mice have substantially increased glucose levels, which indicates that PRDC might play a part in regulation of glucose homeostasis and insulin sensitivity. This grant proposal builds on our previous findings and will use transgenic and tissue-specific knockout mice, together with modern techniques of molecular and cellular biology to explore mechanisms of PRDC in regulation of glucose homeostasis and its inhibition of BMP signalling pathway leading to enhanced insulin sensitivity. Furthermore, longitudinal cohort study in community adults as well as exercise intervention study will also be used to examine the role of PRDC in glucose metabolism in humans. This proposed study has the potential to shed new light on etiological mechanisms of type 2 diabetes and to identify novel therapeutic targets for the disease.