| First Author | Xing C | Year | 2023 |
| Journal | Biochem Pharmacol | Volume | 216 |
| Pages | 115775 | PubMed ID | 37659738 |
| Mgi Jnum | J:340591 | Mgi Id | MGI:7528382 |
| Doi | 10.1016/j.bcp.2023.115775 | Citation | Xing C, et al. (2023) Eicosapentaenoic acid metabolites promotes the trans-differentiation of pancreatic alpha cells to beta cells. Biochem Pharmacol 216:115775 |
| abstractText | 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. |
