金芪降糖片是临床上治疗糖尿病的中药制剂，通过改善胰岛素敏感性降低血糖，但对胰高血糖素反应介导的肝糖异生的作用所知甚少。神经酰胺蓄积导致胰岛素抵抗和肝脏脂质蓄积，但和肝糖异生的关系尚未建立。本课题拟以抑制肝胰高血糖素紊乱下神经酰胺生成为切入点，探讨金芪降糖片抑制肝糖异生的作用和机制。本课题主要研究内容：1）沿经典或非经典NF-κB信号通路确认胰高血糖素通过神经酰胺合成酶5/C16:0型神经酰胺合成放大肝糖异生的作用；2）考察金芪降糖片抑制肝胰高血糖素反应阻断C16:0型神经酰胺蓄积的作用，并在Akt/FoxO1转录调节水平深入调查其抑制肝糖输出的作用机制；3）系统研究金芪降糖片活性成分的交互作用，发现可能存在的协同成分组合。本研究将从肝胰高血糖素反应和神经酰胺代谢角度揭示金芪降糖片纠正代谢紊乱新机制，为拓展其在治疗代谢紊乱性疾病中的应用提供更好地支持。

The preparation of Jinqi Jiantang Pian (JQJTP) is now prescribed in the clinic for the treatment of diabetes, lowering hyperglycaemia by improving insulin sensitivity; however, the implication in glucagon-mediated hepatic gluconeogenesis remains to be elucidated. Although it is well known that ceramide accumulation induces insulin resistance and hepatic lipid deposition, the contribution to gluconeogenesis has not been established. This study is designed to investigate the role of JQJTP in gluconeogenesis suppression from the aspect of ceramide accumulation responding to hepatic glucagon response: 1) whether NF-κB-dependent inflammatory signaling (canonical and non-canonical) mediates C16:0 production by ceramide synthase 5 (CerS5) to promote hepatic gluconeogenesis; 2) by restraining hepatic glucagon response, if JQJTP could prevent C16:0 ceramide accumulation and reduce hepatic glucose output by regulation of Akt/FoxO1；3) JQJTP is multicomponent and multifunctional, and therefore, it is important to find the potential synergy component from the interactions in the regulation. From the aspect of hepatic glucagon response and ceramide metabolism, this study will provide new insight into to mechanism by which JQJTP decreases hyperglycaemia, having a contribution to the better application in the management of metabolic disorders.