Abstract
Objectives
To evaluate the effect of arachidonic acid (AA) in the pathobiology of chemical-induced type 1 and type 2 diabetes mellitus in experimental animals.
Methods
In vitro studies were performed using RIN 5F cells and animal studies in 3–4 week old Wistar rats. Alloxan and streptozotocin (STZ) were used to induce type 1 diabetes and STZ employed to induce type 2 diabetes mellitus. RIN5F cell proliferation was measured using MTT assay. Establishment of alloxan and STZ-induced diabetes in animals was confirmed by measuring plasma glucose levels. Plasma insulin, IL-6, TNF levels were measured by ELISA. Expression of cyclo-oxygenase-2, lipoxiygenase, NF-kB and IkB genes was performed in pancreatic and adipose tissues.
Results
Alloxan and STZ-induced cytotoxicity to RIN5F cells was inhibited by arachidonic acid that was not blocked by both COX and LOX enzymes. Alloxan and STZ-induced type 1 diabetes mellitus and STZ-induced type 2 diabetes was prevented by arachidonic acid treatment. Plasma levels of glucose, insulin, IL-6 and TNF and expressions of NF-kB, IkB, COX-2, LOX in pancrreatic and adipose tissues and lipocalin-2 in adipose tissue were restored to normal by arachidonic acid treatment. AA treatment enhanced plasma lipoxin A4 (LXA4) levels. LXA4 also prevented both type 1 and type 2 diabetes induction by STZ.
Conclusions
AA prevented the development of both type 1 and type 2 diabetes mellitus in Wistar rats and protected pancreatic beta cells form the cytotoxicity of alloxan and STZ. AA showed strong anti-inflammatory actions. AA seems to bring about its anti-inflammatory and anti-diabetic actions by enhancing LXA4 formation.
Funding Sources
None.
Dysregulation of PI3K-Akt-mTOR pathway in brain of streptozotocin-induced type 2 diabetes mellitus in Wistar rats