Streptozotocin-pancreatic damage in the rat: modulatory effect of 15-deoxy delta12,14-prostaglandin j(2) on nitridergic and prostanoid pathway.
15-deoxy-delta (12,14)prostaglandin J(2) (15d-PGJ(2)) has been identified as a natural ligand of the PPARgamma 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 beta 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 < 0.01). 15d-PGJ(2) 10(-5)M inhibits cNOS and iNOS activity both in control and diabetic islets (P < 0.05). Nitrate/nitrite and PGE(2) levels are higher in diabetic than in control islets (P < 0.05 and P < 0.01, respectively). 15d-PGJ(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 PPARgamma antagonist, seems to act as a PPARgamma 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 < 0.05). Our observations suggest that 15d-PGJ(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.
González
Elida
E
Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), CSIC, Barcelona, Spain. elidate@arnet.com.ar
Jawerbaum
Alicia
A
Sinner
Débora
D
Pustovrh
Carolina
C
White
Verónica
V
Capobianco
Evangelina
E
Xaus
Carme
C
Peralta
Carmen
C
Roselló-Catafau
Joan
J
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D011458:Prostaglandins E / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D009566:Nitrates; D009573:Nitrites; D011458:Prostaglandins E; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D015230:Prostaglandin D2