Arachidonic acid and lipoxin A4 as possible endogenous anti-diabetic molecules

In both type 1 and type 2 diabetes mellitus, increased production of pro-inflammatory cytokines and reactive oxygen species (ROS) occurs that induce apoptosis of beta cells and cause peripheral insulin resistance respectively though the degree of their increased production is higher in type 1 and less in type 2 diabetes mellitus. Despite this, the exact mechanism(s) that lead to increased production of pro-inflammatory cytokines: interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) and ROS is not known. Studies showed that plasma concentrations of arachidonic acid (AA) and lipoxin A(4) (LXA(4)) are low in alloxan-induced type 1 diabetes mellitus in experimental animals and patients with type 2 diabetes mellitus. Prior administration of AA, eicosapentaenoic and docosahexaenoic acids (EPA and DHA, respectively) and transgenic animals that produce increased amounts of EPA and DHA acids were protected from chemical-induced diabetes mellitus that was associated with enhanced formation of LXA(4) and resolvins, while protectin D-1 ameliorated peripheral insulin resistance. AA, LXA(4), resolvins and protectins inhibit IL-6 and TNF-alpha production and suppress ROS generation. Thus, AA and lipoxins, resolvins and protectins may function as endogenous anti-diabetic molecules implying that their administration could be useful in the prevention and management of both types of diabetes mellitus. (c) 2012 Elsevier Ltd. All rights reserved.