miR-378a-3p靶向PI3K/AKT信号通路介导小米桃叶珊瑚苷调控糖代谢的分子机制

小米是我国的主要杂粮作物，种植面积和产量均居世界首位。申请人前期研究证实小米具有改善糖代谢的功能，并且首次在小米中发现高含量桃叶珊瑚苷。目前有关桃叶珊瑚苷调控糖代谢的作用机制尚未被阐明，而miRNAs介导的信号通路是机体维持糖代谢稳态的关键途径。据此，本项目拟以前期研究发现的miR-378a-3p和PI3K/AKT信号通路为切入点，评价小米桃叶珊瑚苷作为新型谷物源生物活性物质的可行性；通过构建miR-378a-3p表达量上调和下调的胰岛素抵抗HepG2细胞，并结合报告基因检测系统，明确miR-378a-3p通过靶向PI3K或AKT参与小米桃叶珊瑚苷降糖反应的调控作用；通过动物实验，解析小米桃叶珊瑚苷调控糖异生和糖原合成的具体过程，阐明并验证其通过miR-378a-3p介导PI3K/AKT信号通路调控糖代谢的分子机制。本项目有助于完善小米降糖理论体系，为日常膳食中改善人们机体健康提供新依据。

Foxtail millet is the main coarse cereal in China, with the largest planting area and yield in the world. Our previous studies have confirmed the hypoglycemic effect of foxtail millet. Morever, high content of aucubin has been found in foxtail millet extract for the first time. At present, the molecular mechanism about aucubin regulating glucose metabolism is still unclear. Signaling pathways mediated by miRNAs are the key regulatory approach to maintain glucose homeostasis. Thus to investigate the hypoglycemic effect and mechanism of foxtail millet aucubin, comprehensive experiments in vitro and in vivo will be fully conducted in the present study. Firstly, the role of foxtail millet aucubin in regulating glucose metabolism will be analyzed to evaluate its feasibility as a new type of cereal bioactive substance. Secondly, the regulatory effect of miR-378a-3p targeting PI3K or Akt will be confirmed in the hypoglycemic response of foxtail millet aucubin by constructing of miR-378a-3p up-regulated and down-regulated insulin resistant HepG2 cells with the reporter gene detection system. Then the specific process of gluconeogenesis and glycogen synthesis regulated by foxtail millet aucubin will be analyzed in diabetic mice. Finally, The molecular mechanism of foxtail millet aucubin regulating glucose metabolism based on miR-378a-3p targeting PI3K/AKT signaling pathways will be clarified. This study will improve the hypoglycemic theoretical system foxtail millet and provide scientific guidance for improving human health in daily diet.