胰高血糖素在维持血糖稳态中和胰岛素发挥同等重要作用。临床发现胰高血糖素调节紊乱与2型糖尿病的发生发展密切相关。申请人前期研究发现三七蒸制成熟三七过程中发生脱糖脱水反应，产生大量稀有皂苷，具有更强的降糖效果，尤其可降低急性胰高血糖素模型小鼠血糖的升高，熟三七总皂苷亦可抑制肝组织内cAMP生成、抑制炎症相关蛋白NF-κB2的表达。本项目提出假说：熟三七总皂苷可调控胰高血糖素/cAMP/ NIK/NF-κB2通路抑制肝糖生成，拟开展以下内容：1）采用胰高血糖素相关动物、细胞模型，评价熟三七总皂苷的体内外降糖作用及对糖异生的影响；2）结合基因沉默与过表达技术，阐明总皂苷对cAMP/NIK/NF-κB2通路的干预作用及对cAMP的调节机制；3）系统研究皂苷间的交互作用，发现熟三七中协同降糖皂苷组合。研究成果将揭示熟三七总皂苷通过调节胰高血糖素相关通路抑制肝糖生成的新机制，为降糖药物发现提供新思路。

Hormone glucagon, as well as insulin, plays an important role in maintaining glucose homeostasis. The development and progression of diabetes mellitus type 2 is closely associated with glucagon dysfunction. Compared with crude notoginseng, steamed notoginseng contains novel rare ginsenosides produced by the stepwise deglycosylation and dehydration during processing. Steamed notoginseng shows significant anti-diabetic effects, which proved via glucagon regulation in vivo. Total ginsenosides can inhibit the activation of cAMP and NF-κB2 in liver, indicating the hypoglycemic effect may be related to the glucagon/cAMP /NIK/NF-κB2 pathway. Based on these previous works, this project is aimed to investigate the hypoglycemic effects of total ginsenosides and its glucagon dependent molecular mechanism. The major contents include：1) a series of glucagon-induced animal and cell models were applied to verify the effects of total ginsenosides on hyperglycemia and gluconeogenesis 2) to elucidate the intervention effect of ginsenosides on glucagon mediated cAMP/NIK/NF-κB2 signaling pathway; 3) to discover the potential interactions among the identical or different structural type ginsenosides. The results will reveal the mechanism of total ginsenosides in maintaining glucagon steady state, and provide new strategies for anti-diabetic drugs discovery.