Arachidonic acid and lipoxinA4 attenuate streptozotocin-induced cytotoxicity to RIN5 F cells in vitro and type 1 and type 2 diabetes mellitus in vivo

•Various polyunsaturated fatty acids (PUFAs), especially arachidonic acid (AA), protected RIN5 F (rat pancreatic β) cells against streptozotocin (STZ)-induced cytotoxicity in vitro.•AA also prevented STZ-induced type 1 (T1DM) and type 2 diabetes mellitus (T2DM) in Wistar rats.•The cytoprotective and antidiabetic action of AA was not blocked by either cyclooxygenase or lipoxygenase inhibitors, indicating that prostaglandins, leukotrienes, and thromboxanes do not have a role in this process.•STZ inhibited the production of lipoxin A4 (LXA4) by RIN5 F cells in vitro and in Wistar rats induced to develop T1- and T2DM in vivo.•AA treatment restored LXA4 levels to normal both in vitro and in vivo.•LXA4 was effective in protecting RIN5 F cells against STZ-induced cytotoxicity and in preventing T1- and T2DM, and it restored expression of Nrf2, Glut2, COX2, and iNOS genes and altered antioxidants to normal.•These results suggest that AA and LXA4 may function as endogenous antidiabetic molecules.