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

Overview

1. Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia
2. Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia
3. Interfaculty Institute for Microbiology and Infection Medicine Tübingen, University of Tübingen, Tübingen, Germany
4. Cluster of Excellence EXC 2124 Controlling Microbes to Fight Infections, University of Tübingen, Tübingen, Germany
5. M3‐Research Center for Malignome, Metabolome and Microbiome, University of Tübingen, Tübingen, Germany

Abstract

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.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

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• doi:10.17632/ptfybnhp5g.1, at the source; found in “Data Availability Statement”

Data Availability Statement

The datasets generated and/or analyzed during the current study are available in the Mendeley Data repository: Knezovic, Ana (2026), “Time‐ and region‐specific effects of intranasal insulin on oxidative stress parameters in the rat brain”, Mendeley Data, V1, doi:https://doi.org/10.17632/ptfybnhp5g.1

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Version 2, 28 September 2026

• Publisher: n/a → Wiley

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 5 keywords, 13 MeSH terms, 2 funders, 56 references.

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This paper

Osmanovic Barilar, J., Vlahov, L., Krsnik, A., Mihalic, L., Babic Perhoc, A., Virag, D., Homolak, J., Salkovic‐Petrisic, M., & Knezovic, A. (2026). Time- and Region-Specific Effects of Intranasal Insulin on Oxidative Stress Parameters in the Rat Brain. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 40(13), e72119. https://doi.org/10.1096/fj.202601712r

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