{
  "abstract": "To respond to protein misfolding in the endoplasmic reticulum (ER), cells trigger the unfolded protein response (UPR) to re-establish proteostasis. However, unresolved UPR results in chronic ER stress, which is critical to the development and advancement of type 2 diabetes mellitus (T2DM), a multifactorial disease whose prevalence has continued to rise. The UPR consists of three transmembrane signaling branches - protein kinase R-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 alpha (IRE1α), which collectively attempts to restore proteostasis, or trigger apoptosis if ER stress persists. Among the three, the IRE1α pathway is the most evolutionarily conserved and serves as a central regulator of UPR signaling through the splicing of X-box binding protein 1 mRNA (XBP1s). In the adaptive mode, XBP1s drives the expression of genes that expand ER capacity and alleviate cellular stress. Conversely, chronic activation of the IRE1α pathway activates the regulated IRE1-dependent decay (RIDD) process, recruits tumour necrosis factor receptor-associated factor 2/c-Jun N-terminal kinase (JNK), and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), with their attendant deleterious effects. Thus, the therapeutic utility of the IRE1α/XBP pathway depends on the duration and extent of UPR as well as tissue and cellular metabolic state. The extensive crosstalk of the pathway with metabolic and inflammatory pathways makes it an attractive therapeutic target. This review examines the role of the IRE1α/XBP1 pathway in T2DM and highlights the potential of modulating the pathway as a novel disease-modifying strategy in the context of the increasing burden of the disease.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Life and Consumer Sciences, University of South Africa, Florida Campus, Johannesburg, 1709, South Africa. obafeot@unisa.ac.za.",
    "Department of Life and Consumer Sciences, University of South Africa, Florida Campus, Johannesburg, 1709, South Africa.",
    "Biochemistry Programme, College of Agriculture, Engineering and Sciences, Bowen University, Iwo, 232101, Nigeria.",
    "Department of Biochemistry, Bamidele Olumilua University of Education Science and Technology, Ikere-Ekiti, Nigeria.",
    "Department of Medical Biochemistry, Afe Babalola University, Km 8.5, Afe Babalola way, Ado-Ekiti 360001, Ekiti State, Nigeria.",
    "Drosophila Research/Drug Metabolism and Toxicology Laboratories, Biochemistry Program, College of Sciences, Afe Babalola University, Km 8.5, Afe Babalola way, Ado-Ekiti 360001, Ekiti, Nigeria."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Olabisi Tajudeen Obafemi",
      "orcid": "0000-0001-8894-9365"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Ademola Olabode Ayeleso"
    },
    {
      "affs": [
        3
      ],
      "name": "Bidemi Emmanuel Ekundayo"
    },
    {
      "affs": [
        4
      ],
      "name": "Blessing Ariyo Obafemi"
    },
    {
      "affs": [
        5
      ],
      "name": "Olusola Bolaji Adewale"
    },
    {
      "affs": [
        1
      ],
      "name": "Sogolo Lucky Lebelo"
    },
    {
      "affs": [
        1
      ],
      "name": "Monde Ntwasa"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/camj558459rq1.bib",
  "cited_by": 1,
  "doi": "10.1007/s11033-026-12876-7",
  "fulltext_url": "https://europepmc.org/articles/PMC13649918",
  "id": "camj558459rq1",
  "issns": [
    "0301-4851",
    "1573-4978"
  ],
  "landing_url": "https://europepmc.org/article/MED/42848256",
  "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",
      "1307|Endoplasmic Reticulum Stress and Disease"
    ]
  ],
  "openalex": "W7220971288",
  "pdf_url": "https://europepmc.org/articles/PMC13649918?pdf=render",
  "pmcid": "PMC13649918",
  "pmid": "42848256",
  "published": "2026-10-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/camj558459rq1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:02Z",
      "native_id": "MED:42848256",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42848256"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Endoplasmic Reticulum Stress and Disease",
      "subfield": "cell-biology"
    }
  ],
  "title": "Targeting the IRE1α/XBP1 pathway in type 2 diabetes mellitus: from ER stress signaling to therapeutic opportunity.",
  "title_text": "Targeting the IRE1α/XBP1 pathway in type 2 diabetes mellitus: from ER stress signaling to therapeutic opportunity.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:02Z",
  "url": "https://research.draconitic.com/paper/camj558459rq1",
  "venue": "Molecular biology reports",
  "versions": []
}