半夏泻心汤有效治疗糖尿病前期（IGR）的机制研究滞后，是其经方特色和优势发挥的瓶颈。前期研究发现调控胰高血糖素样肽-1（GLP-1）/胰岛素分泌和葡萄糖运载蛋白2（GLUT2）表达是体现方剂多靶疗效的关键作用，契合针对糖稳态失衡多环节干预的研究热点。依据“肠/胰甜味受体（STRs）介导的GLP-1/胰岛素分泌和GLUT2表达，在糖稳态维持和失衡中起重要作用”的新近进展结合方剂能调控肠/胰STRs信号通路多个环节的预实验，提出“半夏泻心汤调控肠/胰STRs信号通路，改善受损的GLP-1/胰岛素分泌和GLUT2表达，多元整合作用改善糖稳态失衡”的假设。拟研究半夏泻心汤对IGR的治疗作用；对GLP-1/胰岛素分泌及GLUT2表达和肠/胰组织与L/β细胞及小肠吸收细胞STRs信号通路的影响；利用干涉手段进行机制反证；阐明半夏泻心汤调控糖稳态失衡的分子机制。为半夏泻心汤治疗/转归IGR提供科学依据。

The underlying mechanism of Ban-xia-xie-xin Decoction for the effective treatment of the impaired glucose regulation (IGR) lags behind its clinical effectiveness, the circumstances in which characteristics and advantages of Ban-xia-xie-xin Decoction are further hindered. Previous investigation have confirmed that Ban-xia-xie-xin Decoction could regulate glucagon-like peptide-1 (GLP-1) secretion, insulin secretion and glucose transporter 2 (GLUT2) expression, which are responsible for the Ban-xia-xie-xin Decoction treatment of IGR. Ban-xia-xie-xin Decoction treatment of IGR with multi-pathways matches the research hotspot for the interventions on glucose homeostasis disorders with different aspects. Based on the fact that recent studies have demonstrated that sweet taste receptors (STRs) signaling pathway in the intestine and pancreatic islet mediates GLP-1 secretion, insulin secretion, and GLUT2 expression, thereby playing an important role in the maintenance of glucose homeostasis, and our preliminary results show that Ban-xia-xie-xin Decoction could regulate STRs signaling pathway in the intestine and pancreatic islet, we further propose the hypothesis that Ban-xia-xie-xin Decoction improves the impaired GLP-1 secretion and insulin secretion, and GLUT2 expression in order to improve glucose homeostasis disorders through regulating the STRs signaling pathway the intestine and pancreatic islet. To prove this hypothesis, our research plans to use in vitro cell model and in vivo animal model to investigate the following contents: i) the therapeutic effects of Ban-xia-xie-xin Decoction on IGR; ii) the effects of Ban-xia-xie-xin Decoction on GLP-1 secretion and insulin secretion, and GLUT2 expression and STRs signaling pathway in L cells, β cells and Caco-2 cells, and the expression of STRs signaling molecules in intestinal and pancreatic tissues; iii) using the pharmacological and genetic interference to demonstrate the participation of STRs signaling pathway. This study clarifies the molecular mechanism of Ban-xia-xie-xin Decoction regulation of glucose homeostasis disorders, which provides the scientific basis for the treatment and reversal of IGR.