Anti-oxidant effect of nitrite in the pancreatic islets of type ۲ diabetic male rats

Objective(s): Nitrite, a nitric oxide (NO) donor, increases insulin secretion from pancreatic islets and has positive metabolic effects in type ۲ diabetes (T۲D). Here, we test the hypothesis of whether nitrite-induced insulin secretion is due to blunting of diabetes-induced oxidative stress in the islets.Materials and Methods: T۲D was created in male rats using a combination of streptozotocin at ۲۵ mg/kg and a high-fat diet. Wistar rats were assigned to ۳ groups (n=۶ in each group), including control, T۲D, and T۲D+nitrite; the latter group consumed drinking water containing sodium nitrite (۵۰ mg/l) for eight weeks. At the end of the study, mRNA levels of NADPH oxidase (Nox۱, ۲, ۳, and ۴), superoxide dismutase (SOD۱, ۲, and ۳), glutathione peroxides (GPX۱ and ۷), glutathione reductase (GR), catalase, thioredoxin (TXN۱ and ۲), and thioredoxin reductase (TXNRD۱) were measured in the isolated pancreatic islets. Results: In the islets of diabetic rats, mRNA expressions of Nox۱, ۲, and ۴ were higher, whereas expressions of SOD۱, ۲, catalase, GPX۱, ۷, GR, and TXN۱ were lower than controls. Nitrite significantly (all P-values<۰.۰۵) decreased gene expression of Nox۱ (۰.۳۹-fold) and Nox۴ (۰.۲۳-fold) and increased gene expression of SOD۱ (۲.۲-fold), SOD۲ (۲.۸-fold), catalase (۲.۷-fold), GPX۱ (۲.۲-fold), GPX۷ (۶.۰-fold), GR (۳.۰-fold), TXN۱ (۲.۱-fold), and TXNRD۱ (۲.۳-fold) in diabetic rats. Conclusion: Nitrite decreased oxidative stress in isolated pancreatic islets of rats with T۲D by suppressing oxidants and augmenting anti-oxidants. These findings favor the notion that nitrite-induced insulin secretion is partially due to decreased oxidative stress.

کلیدواژه ها:

Nitric oxide ، Nitrite ، Oxidative stress ، Pancreatic islets ، Rat ، Type ۲ diabetes