Insulin-induced oxidative stress in the brain is nitric oxide-dependent

Abstract

Insulin is known to increase brain nitric oxide (NO) level and to cause oxidative stress but the relationship between these phenomena has not been well elucidated. This study aimed to examine the role of NO in the insulin-NO-oxidative stress axis in the brain. Mice were grouped into four (n = 5) and treated for seven days with 0.2 ml deionized water (control); 10 I.U./kg insulin; 10 I.U./kg insulin + 50 mg/kg L-NAME; and 50 mg/kg L-NAME. The mice were anaesthesized using ketamine + xylazine and sacrificed at the end of the study. Forebrain was immediately harvested from which brain homogenates were prepared in order to determine NO and malondialdehyde (MDA) concentrations as well as glutathione peroxidase (GPx) activity using commercially available kits. Data were processed using IBM SPSS Statistics 20.0. Nitric oxide values were higher in the insulin group (p < 0.05) but not in the insulin+L-NAME (p > 0.05) group when compared with the control. Values of MDA in the insulin and insulin+L-NAME groups were higher (p < 0.05) and the same (p > 0.05), respectively, than those in the control group. The activity of GPx in the insulin group was lower (p < 0.05) than, but that of the insulin+L-NAME was the same (p > 0.05) as in the control group. Insulin increased NO concentration and oxidative stress as indicated by increased MDA concentration and decreased GPx activity in the treated mice. This insulin effect was reversed by L-NAME (a non-specific NO inhibitor). These data suggest that insulin increased oxidative stress in the brain through an NO-dependent process. Insulin treatment may be harmful to the brain.