Insulin treatment increases brain nitric oxide and oxidative stress, but does not affect memory function in mice

Abstract

Insulin increases brain nitric oxide (NO) level but the mechanism and the significance of the effect on memory are not fully understood. This study aimed to demonstrate the mechanism of insulin-induced increase in oxidative stress (OS) and its consequences on learning and memory. Twenty four mice were assigned to groups (n = 6) and treated daily for seven days with water (control), insulin, insulin+Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) and L-NAME, respectively. Memory was assessed using Y-maze; NO, malondialdehyde (MDA) and glutathione peroxidase (GPx) in brain homogenate were also determined. There was no difference between the groups in the number of entries into the arms and time spent in them, and in number of and percentage alternations performed by the mice, indicating normal memory function of the control and treated mice. NO level in the insulin group was higher compared to the control (p = .018), while those of the other groups were statistically the same compared to the control group. MDA values in the insulin group were higher (p = .001) than those of the control, while those of the other groups were statistically the same compared to those of the control group. GPx activity in the insulin group was lower compared to control (p = .004), while that of the other groups was not significantly different compared to control. It was concluded that insulin treatment increased brain level of NO and OS through increased malondialdehyde level and glutathione peroxidase activity; insulin treatment did not affect long-term visuo-spatial and short-term working memory in the animals. Insulin treatment may have deleterious effects on the brain through increased NO and OS levels.