Eicosapentaenoic acid代谢产物促进胰岛α细胞转分化为胰岛β细胞的作用研究  

Effects of metabolites of eicosapentaenoic acid on promoting transdifferentiation of pancreaticαcells into pancreatic β cells

作　　者：邢朝凤 唐敏怡 徐绮华 王帅 张宗猛 赵子建 穆云萍 李芳红 XING Chao-feng;TANG Min-yi;XU Qi-hua;WANG Shuai;ZHANG Zong-meng;ZHAO Zi-jian;MU Yun-pin;LI Fang-hong(School of Biomedical and Pharmaceutical Sciences,Guangdong University of Technology,Guangzhou 510006,China)

机构地区：[1]广东工业大学生物医药学院,广东广州510006

出　　处：《中国药理学通报》2024年第1期31-38,共8页Chinese Pharmacological Bulletin

基　　金：国家重点研发计划项目(No 2018YFA0800603);广东省重点领域研发计划项目(No 2019B020201015);广东省“珠江人才计划”项目(No 2016ZT06Y432)。

摘　　要：目的 探讨eicosapentaenoic acid(EPA)代谢产物促进胰岛α细胞向β细胞转分化的作用。方法 雄性C57BL/6J小鼠连续5 d腹腔注射60 mg/kg链脲佐霉素(streptozocin, STZ)构建1型糖尿病(T1DM)小鼠模型,2周后随机分为模型组、97%EPA饮食干预组、75%鱼油(50%EPA+25%DHA)饮食干预组,每周检测随机血糖;模型到期后,通过免疫荧光染色观察小鼠胰腺中胰岛β细胞再生情况。提取tdTomato荧光蛋白特意标记α细胞的小鼠(GCGicre小鼠与Rosa26tdTomato小鼠杂交获得)胰岛,加入1 mmol·L^(-1)STZ诱导β细胞凋亡,添加EPA代谢产物,培养48 h后,利用荧光染色观察胰岛素和tdTomato荧光的表达。在小鼠胰岛α细胞系αTC1培养基中添加EPA代谢产物,48 h后,利用荧光染色观察胰岛素和胰高血糖素的表达。结果 EPA和鱼油饮食干预均可明显降低T1DM小鼠的血糖水平,改善葡萄糖稳态,且胰腺中出现胰岛素和胰高血糖素共定位细胞;EPA代谢产物引起已发生β细胞凋亡的小鼠胰岛中发生tdTomato荧光蛋白和胰岛素共定位;EPA代谢产物可促进胰岛αTC1细胞系细胞分泌胰岛素。结论 EPA及其代谢产物可通过促进胰岛α细胞转分化为β细胞,进而增加胰岛素的分泌,缓解T1DM小鼠的高血糖症状。Aim To investigate the role of metabolites of eicosapentaenoic acid(EPA)in promoting the transdifferentiation of pancreaticαcells toβcells.Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin(STZ)for five consecutive days to establish a type 1 diabetes(T1DM)mouse model.After two weeks,they were randomly divided into model groups and 97%EPA diet intervention group,75%fish oil(50%EPA+25%DHA)diet intervention group,and random blood glucose was detected every week;after the model expired,the regeneration of pancreaticβcells in mouse pancreas was observed by immunofluorescence staining.The islets of mice(obtained by crossing GCG icre mice and Rosa 26tdTomato mice)specially marked with tdTomato fluorescent protein was extracted,1 mmol·L^(-1) STZ was added to induce apoptosis ofβcells,EPA metabolites were addded,cultured for 48 hours,and fluorescent staining was used to observe insulin and tdTomato expression of fluorescence.EPA metabolites were added to the medium of mouse isletαcell lineαTC1,and after 48 hours,the expressions of insulin and glucagon were observed by fluorescent staining.Results Both EPA and fish oil dietary intervention could significantly reduce blood glucose levels in T1DM mice,improve glucose homeostasis,and co-localize cells of insulin and glucagon in pancreas.Co-localization of tdTomato fluorescent protein and insulin occurred.EPA metabolites could promote insulin secretion from pancreaticαTC1 cell line cells.Conclusion EPA and its metabolites can alleviate hyperglycemia in T1DM mice by promoting the transdifferentiation of pancreaticαcells intoβcells,thus increasing insulin secretion.

关 键 词：EPA 1型糖尿病 胰岛Α细胞 胰岛Β细胞 转分化 代谢产物 

分 类 号：R-332[医药卫生] R151.41R322.57R347.8R587.1