二十碳五烯酸
内科学
内分泌学
PDX1型
多不饱和脂肪酸
胰岛素
胰岛
链脲佐菌素
生物
胰高血糖素
糖尿病
化学
小岛
脂肪酸
生物化学
医学
作者
Chengjuan Xing,Minyi Tang,Jianqin Yang,Shuai Wang,Qihua Xu,Wenbin Feng,Yunping Mu,Fanghong Li,Allan Z. Zhao
标识
DOI:10.1016/j.bcp.2023.115775
摘要
Type 1 diabetes mellitus (T1DM) is characterized by life-threatening absolute insulin deficiency. Although ω-3 polyunsaturated fatty acids (PUFAs) displayed significant anti-hyperglycemic activity, the insulinotropic effects of their metabolites remain unknown. In this study, we took advantage of a transgenic model, mfat-1, that overexpresses an ω-3 desaturase and can convert ω-6 PUFAs to ω-3 PUFAs. Eicosapentaenoic acid (EPA) was sharply elevated in the pancreatic tissues of mfat-1 transgenic mice compared with wild-type (WT) mice. In contrast to the WT mice, the mfat-1 transgenics did not develop overt diabetes and still maintained normal blood glucose levels and insulin secretion following streptozotocin-treatment. Furthermore, under the condition of pancreatic β-cell damage, co-incubation of the metabolites of EPA produced from the CYP 450 pathway with isolated islets promoted the overexpression of insulin as well as β-cell specific markers, pdx1 and Nkx6.1 in pancreatic α-cells. Addition of EPA metabolites to the cultured glucagon-positive α-cell lines, a series of pancreatic β-cell markers were also found significantly elevated. Combined together, these results demonstrated the effects of ω-3 PUFAs and their metabolites on the trans-differentiation from α-cells to β-cells and its potential usage in the intervention of T1DM.
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