Time- and Region-Specific Effects of Intranasal Insulin on Oxidative Stress Parameters in the Rat Brain

Understanding how intranasal insulin affects brain signaling and metabolism is essential for elucidating its therapeutic potential in neurodegenerative disorders with underlying metabolic dysfunction, such as Alzheimer's disease (AD). Oxidative stress, which increases with aging, has been observed in both AD and Type 2 diabetes, indicating a potential link between oxidative stress, brain insulin resistance and cognitive impairment. This study examined how intranasal insulin affects redox homeostasis across different brain regions and time points. Male Wistar rats received 2 IU of insulin intranasally and were sacrificed 3, 7.5, 15, 30, 60, and 120 min post-administration. Six animals served as intact controls. Redox homeostasis was assessed by measuring lipid peroxidation, total reductive capacity, thiol concentrations, and superoxide dismutase activity in plasma, nasal epithelia, and brain regions. The results were correlated with insulin signaling markers. Intranasal insulin induced rapid but regionally diverse redox responses. The most pronounced alterations occurred in nasal epithelia, where respiratory and olfactory regions exhibited distinct and opposing patterns. In the brain, significant alterations, particularly in thiol-related parameters, were observed across multiple regions including cortices, hippocampus, hypothalamus, olfactory bulb, and cerebellum. Plasma redox parameters remained largely unchanged, supporting the predominantly central action of intranasally delivered insulin. Correlation analyses revealed associations between oxidative stress markers and insulin signaling parameters, suggesting complex interactions between metabolic signaling pathways and redox regulation. These findings demonstrate that intranasal insulin modulates redox homeostasis in a rapid, region-specific, and time-dependent manner, highlighting the importance of spatial and temporal factors in insulin-mediated regulation of brain oxidative balance.