Effects of metformin on oxidative stress, adenine nucleotides balance, and glucose-induced insulin release impaired by chronic free fatty acids exposure in rat pancreatic islets

摘要: Background: In rat pancreatic islets, chronic exposure to high free fatty acid (FFA) levels impairs insulin secretion and β cell mass. The mechanisms underlying this defect are not completely understood. Since islets have intrinsically low anti-oxidant enzyme defense, oxidative stress might be responsible for damage. Aim: study, we investigated if FFA could induce in metformin reverse adverse effects. Material methods: We cultured the presence or absence of (oleate/palmitate 2:1, 2 mM) 72 h. some experiments, used (2.5 µg/ml) during last 24 Results: our model, glucose-stimulated release was markedly reduced (p<0.005) after exposure, ATP/ADP ratio altered (p<0.05). observed a significant increase reactive oxygen species (ROS) (p<0.001), malondialdehyde lipid peroxidation product (p<0.01) nitric oxide (NO) culture media (p<0.001). Inducible NO synthase (iNOS) heat shock protein-70 (HSP-70) protein expression were also increased (p<0.001 p<0.01, respectively). When present h culture, restored, normalized. ROS production, peroxidation, iNOS HSP-70 had decreased. Conclusions: These data indicate that, induces that metformin, by reducing effect, may direct beneficial effect on impaired lipotoxicity.