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Transcriptomics and proteomics characterizing the antioxidant mechanisms of semaglutide in diabetic mice with cognitive impairment

  • Authors:
    • Ying Yang
    • Lulu Song
    • Liping Yu
    • Jinping Zhang
    • Bo Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, China‑Japan Friendship Hospital, Beijing 100029, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 56
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    Published online on: January 30, 2025
       https://doi.org/10.3892/ijmm.2025.5497
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Abstract

The aim of the present study was to investigate the neuroprotective effects of semaglutide in diabetes‑associated cognitive decline (DACD), while also exploring the underlying mechanisms targeting anti‑oxidative effects. The present study evaluated the antioxidant properties of semaglutide using a DACD model of inflammation. To investigate the underlying mechanisms, omics technologies were employed. Comprehensive transcriptomic and proteomic analysis of the cells was conducted to identify the pathways responsible for the observed antioxidant effects. Semaglutide demonstrated the potential to enhance learning and memory functions while mitigating hippocampal pathological damage. RNA‑sequencing and data‑independent acquisition proteomics analyses identified 13,511 differentially expressed genes and 588 differentially expressed proteins between the control and type 2 diabetes mellitus (T2DM) groups. In addition, 1,378 genes and 2,394 proteins exhibited a differential expression between the T2DM and semaglutide (10 µg/kg) treatment groups. A combined transcriptomic and proteomic analysis unveiled 40 common pathways. Acyl‑CoA oxidase 1 (ACOX1) was observed to be activated during oxidative stress and subsequently suppressed by semaglutide. Of note, the antioxidant and anti‑apoptotic properties of semaglutide in high glucose (HG) conditions were partially reversed upon ACOX1 overexpression. Overall, the present data provided molecular evidence to elucidate the physiological connections between semaglutide and neuronal function, and contribute to clarifying the role of semaglutide in combating oxidative stress and HG‑induced cognitive impairment.
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Spandidos Publications style
Yang Y, Song L, Yu L, Zhang J and Zhang B: Transcriptomics and proteomics characterizing the antioxidant mechanisms of semaglutide in diabetic mice with cognitive impairment. Int J Mol Med 55: 56, 2025.
APA
Yang, Y., Song, L., Yu, L., Zhang, J., & Zhang, B. (2025). Transcriptomics and proteomics characterizing the antioxidant mechanisms of semaglutide in diabetic mice with cognitive impairment. International Journal of Molecular Medicine, 55, 56. https://doi.org/10.3892/ijmm.2025.5497
MLA
Yang, Y., Song, L., Yu, L., Zhang, J., Zhang, B."Transcriptomics and proteomics characterizing the antioxidant mechanisms of semaglutide in diabetic mice with cognitive impairment". International Journal of Molecular Medicine 55.4 (2025): 56.
Chicago
Yang, Y., Song, L., Yu, L., Zhang, J., Zhang, B."Transcriptomics and proteomics characterizing the antioxidant mechanisms of semaglutide in diabetic mice with cognitive impairment". International Journal of Molecular Medicine 55, no. 4 (2025): 56. https://doi.org/10.3892/ijmm.2025.5497
Copy and paste a formatted citation
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Spandidos Publications style
Yang Y, Song L, Yu L, Zhang J and Zhang B: Transcriptomics and proteomics characterizing the antioxidant mechanisms of semaglutide in diabetic mice with cognitive impairment. Int J Mol Med 55: 56, 2025.
APA
Yang, Y., Song, L., Yu, L., Zhang, J., & Zhang, B. (2025). Transcriptomics and proteomics characterizing the antioxidant mechanisms of semaglutide in diabetic mice with cognitive impairment. International Journal of Molecular Medicine, 55, 56. https://doi.org/10.3892/ijmm.2025.5497
MLA
Yang, Y., Song, L., Yu, L., Zhang, J., Zhang, B."Transcriptomics and proteomics characterizing the antioxidant mechanisms of semaglutide in diabetic mice with cognitive impairment". International Journal of Molecular Medicine 55.4 (2025): 56.
Chicago
Yang, Y., Song, L., Yu, L., Zhang, J., Zhang, B."Transcriptomics and proteomics characterizing the antioxidant mechanisms of semaglutide in diabetic mice with cognitive impairment". International Journal of Molecular Medicine 55, no. 4 (2025): 56. https://doi.org/10.3892/ijmm.2025.5497
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