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Streptozotocin-pancreatic damage in the rat: Modulatory effect of 15-deoxy delta 12,14-prostaglandin J2 on nitridergic and prostanoid pathway

AutorGonzález, Elida; Jawerbaum, Alicia; Sinner, Débora; Pustovrh, Carolina; White, Verónica; Capobianco, Evangelina; Xaus, Carme ; Peralta, Carmen; Roselló-Catafau, Joan
Palabras clavePPARγ
Pancreatic islets
Diabetes
15-deoxy Δ 12,14-PGJ 2
Nitric oxide
Prostaglandins
Fecha de publicación2002
EditorAcademic Press
CitaciónNitric Oxide - Biology and Chemistry 6(2): 214-220 (2002)
Resumen15-deoxy-delta 12,14prostaglandin J2 (15d-PGJ2) 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-PGJ2 may regulate the production of these proinflammatory compounds that lead to β cell destruction in the diabetic pathology. In this work we evaluated Ca2+-dependent (cNOS) and Ca2+-independent (iNOS) activity, nitrate/nitrite levels, 15-dPGJ2 and prostaglandin E2 (PGE2) levels in isolated pancreatic islets, and 15d-PGJ2 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 < 0.01). 15d-PGJ2 10-5M inhibits cNOS and iNOS activity both in control and diabetic islets (P < 0.05). Nitrate/nitrite and PGE2 levels are higher in diabetic than in control islets (P < 0.05 and P < 0.01, respectively). 15d-PGJ2 10-5M decreases nitrate/nitrite and PGE2 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-PGJ2 production is lower in islets from diabetic animals compared to control (P < 0.05). Our observations suggest that 15d-PGJ2 is able to diminish the production of vasoactive proinflammatory agents in pancreatic islets. The diminished 15d-PGJ2 levels in the diabetic islets are probably related to the diminished capacity to limit the inflammatory response due to experimental diabetes in the rat. © 2001 Elsevier Science (USA).
Versión del editorhttp://dx.doi.org/10.1006/niox.2001.0405
URIhttp://hdl.handle.net/10261/114095
DOI10.1006/niox.2001.0405
Identificadoresdoi: 10.1006/niox.2001.0405
issn: 1089-8603
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