Streptozotocin-Pancreatic Damage in the Rat: Modulatory Effect of 15-Deoxy Delta12,14-Prostaglandin J2 on Nitridergic and Prostanoid Pathway

Abstract 15-deoxy-delta 12,14 prostaglandin J 2 (15d-PGJ 2 ) has been identified as a natural ligand of the PPARγ subtype. PPAR activation in nonadipose tissues seems to inhibit iNOS and COX2 expression. Vasoactive compounds like nitric oxide and prostaglandins are increased in pancreatic tissue from streptozotocin-diabetic rats. We hypothesize that 15d-PGJ 2 may regulate the production of these proinflammatory compounds that lead to β cell destruction in the diabetic pathology. In this work we evaluated Ca 2+ -dependent (cNOS) and Ca 2+ -independent (iNOS) activity, nitrate/nitrite levels, 15-dPGJ 2 and prostaglandin E 2 (PGE 2 ) levels in isolated pancreatic islets, and 15d-PGJ 2 levels in plasma from control and streptozotocin-diabetic rats. Our results show that cNOS is predominant in control, while iNOS isoform is increased in the diabetic islets ( P 2 10 −5 M inhibits cNOS and iNOS activity both in control and diabetic islets ( P 2 levels are higher in diabetic than in control islets ( P P 2 10 -5 M decreases nitrate/nitrite and PGE 2 levels both in control and in diabetic islets. Bisphenol A diglycidyl ether (BADGE), a recently described PPARγ antagonist, seems to act as a PPARγ agonist, diminishing nitrate/nitrite and PGE2 levels in control and diabetic islets. 15d-PGJ 2 production is lower in islets from diabetic animals compared to control ( P 2 is able to diminish the production of vasoactive proinflammatory agents in pancreatic islets. The diminished 15d-PGJ 2 levels in the diabetic islets are probably related to the diminished capacity to limit the inflammatory response due to experimental diabetes in the rat.