慢性炎症导致胰岛β细胞功能受损在2型糖尿病发生发展中起重要作用。NLRP3炎症小体作为主要感受代谢应激受体，异常激活会引起caspase-1形成及IL-1β过度表达，促进糖尿病进程。前期发现脂毒性会造成β细胞功能受损，细胞内NLRP3，IL-1β，caspase-1表达水平明显上调。同时发现褐藻多糖硫酸酯(Fucoidan)能够降低糖尿病大鼠血糖和增强胰岛素耐受。经Fucoidan制备的新型甘露葡萄糖醛酸多/寡糖(GM)有抗氧化活性，能促进HepG2细胞葡萄糖消耗。提示GM可用于糖尿病治疗和胰岛β细胞功能改善。本项目以细胞、胰岛、普通小鼠和NLRP3-/-小鼠为基础，利用RNA-Seq转录组，Western blot和Co-IP蛋白分析，免疫组化和电镜分析，GSIS功能分析，开发活性多/寡糖，阐明其通过抑制NLRP3炎症小体改善胰岛β细胞功能的机制，为海洋原创性药物开发提供基础和治疗靶点。

Pancreatic β cell dysfunction caused by low-grade inflammation plays an important role in type 2 diabetes. NLRP3 inflammasome, as the key sensing receptor of metabolic stress, activates abnormally resulting in overexpression of caspase-1 and IL-1β. Our previous study showed the gene and protein expression of NLRP3, IL-1β, and caspase-1 were significantly upgrade owing to lipid toxicity. Further study indicated Fucoidan can ameliorate blood glucose and improve insulin sensitivity in diabetic rats. Glucuronomannan/glucuronomannan oligosaccharides (GM) were obtained after separation and purification from Fucoidan. As new structural saccharine, antioxidant activity and glucose consumption of HepG2 cell were confirmed. Based on these results, we hypothesize that GM can treat diabetes and improve insulin secretion of beta cell. In this study, we plan to elucidate the mechanism of ameliorating beta cell function by reducing inflammation. Multiple approaches, including RNA-Seq based on transcriptome analysis, western blot and Co-IP based on protein and signaling pathway analysis, immunohistochemistry and electron microscopy based on pancreatic islets morphology and structure analysis, and glucose stimulated insulin secretion, will be used to examine the functional saccharine and expound the mechanism of relieving diabetes by NLRP3 inflammasome. Successful completion of this study will provide the basic and therapeutic targets for marine original drug development.