Daniel Roberto Pomaro1, Silvia Saiuli Miki Ihara1, Aparecida Emico Hirata2, Tatiana Helfenstein3, Maria Cristina Izar3, Tania Leme da Rocha Martinez4*, Anita L R Saldanha4, Lech Michal Szymanski4 and Francisco Antonio Helfenstein Fonseca3

Background: Diabetes Mellitus is a major risk factor for vascular disease and the imbalance of the renin-angiotensin system (RAS) exerts deleterious effects on various organs, and so, the use of angiotensin-converting enzyme (ACE) inhibitor or angiotensin II type 1 receptor (AT1) blockers may have a beneficial effect. The activation of RAS in the pancreas islet may induce the synthesis of reactive oxygen species, causing oxidative stress-induced B cell dysfunction.
Objective: The effect of the ACE inhibitor was analyzed in pancreas of diabetic and hypercholesterolemic rabbits in in vivo model, and in isolated rabbit pancreatic islets incubated with high glucose medium in in vitro study. Methods: We performed a study on tissue samples of pancreas of alloxan-induced diabetic rabbits which have also become hypercolesterolemic through a rich cholesterol chow. The animals were divided into four groups according to glucose levels (Group I=432±45 mg/dL, Group II=514±40 mg/dL, Group III=149±09 mg/dL, Group IV=156±10 mg/dL). The rabbits in groups II and IV received quinapril (30 mg/day) in their food and all animals received a diet enriched with 0.5% cholesterol for 12 weeks. The histopathology and histomorfometry of pancreas islets were realized in specimens stained by hematoxilin-eosin and immunohistochemical reaction with insulin antibody. In in vitro study, the production of superoxide was determined by hidroetidina oxidation and the fluorescence stimulated and quantified by confocal microscope.
Results: In in vivo study, destruction of beta cells was observed in diabetic animals, however, differences weren’t observed in groups treated with ACE inhibitor analyzed by immunohistochemistry. In in vitro study, reduced production of superoxide was observed in the pancreatic islets treated with IECA in medium with low glucose concentration.
Conclusion: The ACE inhibitor impaired the production of superoxide in islets isolated from rabbits, mainly in the presence of normal concentration of glucose, suggesting that the blockade of RAS may attenuate the deleterious actions of Angiotensin II on pancreatic islet structure.

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