Eicosapentaenoic acid metabolites promotes the trans-differentiation of pancreatic α cells to β cells

Type 1 diabetes mellitus (T1DM) is characterized by life-threatening absolute insulin deficiency. Although omega-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 omega-3 desaturase and can convert omega-6 PUFAs to omega-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 beta-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 beta-cell specific markers, pdx1 and Nkx6.1 in pancreatic alpha-cells. Addition of EPA metabolites to the cultured glucagon-positive alpha-cell lines, a series of pancreatic beta-cell markers were also found significantly elevated. Combined together, these results demonstrated the effects of omega-3 PUFAs and their metabolites on the trans-differentiation from alpha-cells to beta-cells and its potential usage in the intervention of T1DM.