栀子具降糖功效，常用于糖尿病治疗。他人及课题组前期研究均发现，栀子口服给药后才可有效降糖，然目前以胰腺为主要靶器官的研究无法阐释其降糖需口服的分子机制。课题组依据前期研究结果认为：栀子口服后对结肠G蛋白偶联胆酸盐受体（Tgr5）-胰高血糖素样肽-1（Glp-1）通路的激活可能是其实现降糖功效的先决条件，也是其口服有效的原因，并提出栀子对结肠Tgr5-Glp-1通路的激活存在2条可能路径:①于结肠直接激活；②于回肠抑制胆酸盐重吸收转运体Asbt，使大量胆酸盐（Tgr5内源性激动剂）排入结肠发挥利胆作用后，激活通路，即“栀子以利胆功效推动降糖功效实现”的新观点。为此，本项目拟对2型糖尿病小鼠进行体内、结肠靶向给药、在体肠孵育和胆汁转流实验并结合Transwell细胞实验，明确栀子激活结肠Tgr5-Glp-1通路发挥降糖作用的具体路径并阐明其机制，为栀子降糖功效的进一步研发和应用奠定基础。

Gardenia jasminoides Ellis (Zhi-zi) with the hypoglycemic effect is commonly used for treatment of diabetes mellitus. The relevant studies and our previous study suggested that Zhi-zi exerting the hypoglycemic effect needs to be orally administrated. However, the existing researches which target pancreas to identify the mechanisms of the hypoglycemic effect of Zhi-zi cannot explain the phenomenon about Zhi-zi achieving the hypoglycemic effect via oral administration. Therefore, according to our precious study, we found that the activation of the signaling pathway that consists of G protein-coupled bile acid receptor (Tgr5) and Glucagon-Like Peptide-1 (Glp-1) in colon position after orally administrated with Zhi-zi is the prerequisite, which is also the major reason for the hypoglycemic effect achievement of Zhi-zi needed oral administration. Moreover, we considered that Zhi-zi activating the Tgr5-Glp-1 pathway should exist two ways: ① Zhi-zi directly activates the pathway at the colon position; ② Zhi-zi promote the most of bile acids to excrete into the colon position via inhibiting the Asbt that is the transporter mediating the reabsorption of bile acid at the ileam position, and then the bile acids as the natural agonists of Tgr5 activate the pathway. This is a novel point we have proposed, " Zhi-zi exerts its hypoglycemic effect with the help of the achievement of its choleretic effect ". Here, we will employ the in vivo experiment, colon-specific drug administration, intestine incubation in situ experiment, bile diversion experiment and Transwell cell experimental system under the condition of type 2 diabetes in mice to identify the way or ways that activate the Tgr5-Glp-1 pathway mentioned above and illuminate the mechanism about the hypoglycemic effect of Zhi-zi. We expect this study can establish a foundation for the research and development of Zhi-zi in the future.