{
  "abstract": "Introduction\n\nPreservation of pancreatic β cells under sustained glucolipotoxicity requires more than limiting cell death, because surviving cells retain stress-associated molecular abnormalities. We tested whether EPA and DHA act through an NRF2-dependent protective program in β-cell models.Methods\n\nMIN6 cells and primary mouse islets were exposed to palmitate plus high glucose with or without EPA, DHA, or EPA+DHA. NRF2 nuclear localization, glutathione homeostasis, oxidative DNA damage, apoptosis, senescence markers, and β-cell maturity proteins were assessed, and NRF2 knockdown was used to test NRF2 dependency. Male C57BL/6J mice with established HFD/STZ diabetes received EPA, DHA, or EPA+DHA; glycemic indices and pancreatic β-cell markers were evaluated.Results\n\nEPA and DHA increased nuclear NRF2, restored glutathione homeostasis, and reduced oxidative DNA damage, apoptotic markers, and senescence markers in both MIN6 cells and primary islets. NRF2 knockdown partially attenuated these responses, indicating that NRF2 contributes to but is not the sole mediator of the in vitro protection. In HFD/STZ mice, EPA/DHA improved glycemic indices, reduced oxidative-stress and apoptotic markers, and preserved insulin-positive β-cell area.Discussion\n\nThese findings identify an NRF2-sensitive program through which EPA and DHA preserve antioxidant capacity, survival, and maturity features of β cells under glucolipotoxic stress. Partial attenuation by NRF2 knockdown and the systemic nature of the HFD/STZ model indicate that additional NRF2-independent mechanisms contribute, and that β-cell specific NRF2 deletion will be needed to establish β-cell autonomous causality in vivo.",
  "abstract_shown": true,
  "affiliations": [
    "The Eighth Affiliated Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), Foshan, Guangdong, China.",
    "Laboratory Animal Center, Sun Yat-sen University, Guangzhou, China.",
    "GuangDong Engineering Technology Research Center of Metabolic Disorders Interdisciplinary Precision Prevention and Digital Healthcare, The Eighth Affiliated Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), Foshan, Guangdong, China.",
    "Center for Reproductive Medicine, the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, China.",
    "Faculty of Health Sciences, University of Macau, Macau, China.",
    "The School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chaofeng Xing"
    },
    {
      "affs": [
        0
      ],
      "name": "Fanghong Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Yan Zou"
    },
    {
      "affs": [
        0
      ],
      "name": "Cheng Song"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Dan Luo"
    },
    {
      "affs": [
        3
      ],
      "name": "Jian Ruan"
    },
    {
      "affs": [
        0
      ],
      "name": "Minyi Tang"
    },
    {
      "affs": [
        4
      ],
      "name": "Qihua Xu"
    },
    {
      "affs": [
        5
      ],
      "name": "Yunping Mu"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Jie Shen"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Allan Zijian Zhao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/87xkcxx946ys6.bib",
  "cited_by": 0,
  "doi": "10.3389/fphys.2026.1948763",
  "fulltext_url": "https://europepmc.org/articles/PMC13682977",
  "id": "87xkcxx946ys6",
  "issns": [
    "1664-042X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42908596",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2746|Pancreatic function and diabetes"
    ]
  ],
  "openalex": "W7220853036",
  "pdf_url": "https://europepmc.org/articles/PMC13682977?pdf=render",
  "pmcid": "PMC13682977",
  "pmid": "42908596",
  "published": "2026-10-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/87xkcxx946ys6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:57Z",
      "native_id": "MED:42908596",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42908596"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Pancreatic function and diabetes",
      "subfield": "surgery"
    }
  ],
  "title": "EPA and DHA engage NRF2 to orchestrate a β-cell resilience circuit suppressing senescence remodeling and sustaining molecular fitness during glucolipotoxic stress.",
  "title_text": "EPA and DHA engage NRF2 to orchestrate a β-cell resilience circuit suppressing senescence remodeling and sustaining molecular fitness during glucolipotoxic stress.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:57Z",
  "url": "https://research.draconitic.com/paper/87xkcxx946ys6",
  "venue": "Frontiers in physiology",
  "versions": []
}