{
  "abstract": "Background: Traditional clinical chemistry views magnesium (Mg2⁺) primarily as a homeostatic marker, with serum levels used to detect overt deficiency. However, emerging evidence indicates that intracellular Mg2⁺ signaling via the transient receptor potential melastatin 7 (TRPM7) chanzyme plays a critical role in pancreatic β-cell function, insulin production, and compensatory responses during metabolic stress. This systematic review synthesizes original research on TRPM7-mediated magnesium signaling as a proposed Mg2⁺-sensing metabolic checkpoint in β-cell biology and its relevance to type 2 diabetes (T2D).\n\nMethods: Following the PRISMA 2020 guideline, a systematic search was conducted in PubMed, Scopus, and Web of Science (inception to May 2026). Only original peer-reviewed studies examining TRPM7 in β-cell function, insulin secretion/synthesis, or compensatory proliferation in obesity/T2D contexts were included.\n\nResults: Five original studies met the strict criteria. One key study demonstrated that β-cell-specific TRPM7 kinase inactivation impairs insulin synthesis and compensatory β-cell proliferation via AKT/ERK signaling, leading to glucose intolerance in obesity despite normal serum Mg2⁺ levels. Supporting studies showed that TRPM7 regulates β-cell development and high-fat-diet-induced proliferation, while Mg2⁺ supplementation partially rescues TRPM7-related deficits (primarily through improved insulin sensitivity and increased β-cell proliferation rather than direct enhancement of glucose-stimulated insulin secretion). Conserved Mg2⁺–TRPM7–mTOR signaling further links this pathway to proliferative capacity.\n\nConclusion: TRPM7 may represent a Mg2⁺-sensing metabolic checkpoint in β-cells, translating intracellular Mg2⁺ availability into adaptive insulin production and compensatory proliferation. This review highlights a major translational gap in clinical chemistry, which currently relies primarily on serum Mg2⁺ measurements and does not capture intracellular Mg2⁺ signaling dynamics. Assessment of TRPM7 function as a candidate functional biomarker could enable earlier detection and more targeted interventions in β-cell failure and T2D.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biochemistry, Adventist University of Central Africa (AUCA); Adventist School of Medicine of East Central Africa (ASOME), Kigali, Rwanda",
    "Department of Physiology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Huye, Rwanda",
    "Department of Microbiology, Adventist University of Central Africa (AUCA); Adventist School of Medicine of East Central Africa (ASOME), Kigali, Rwanda",
    "Department of Intensive Care Unit, Centre Hospitalier Universitaire de Kigali / University Teaching Hospital of Kigali (CHUK), Kigali, Rwanda",
    "Vice Dean, Adventist School of Medicine of East-Central Africa (ASOME), Kigali, Rwanda",
    "Associate Dean of Medical Education, Adventist School of Medicine of East-Central Africa (ASOME), Kigali, Rwanda"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Marie Gorette Kampire"
    },
    {
      "affs": [
        1
      ],
      "name": "Jean Claude Hakizimana",
      "orcid": "0009-0002-4749-1540"
    },
    {
      "affs": [
        2
      ],
      "name": "Joseph Mucumbitsi"
    },
    {
      "affs": [
        2
      ],
      "name": "Callixta Kaneza"
    },
    {
      "affs": [
        2
      ],
      "name": "Bushobozi Themistocles"
    },
    {
      "affs": [
        3
      ],
      "name": "Sophie Mukantwari"
    },
    {
      "affs": [
        4
      ],
      "name": "Jean Mfizi Ngaboyishema"
    },
    {
      "affs": [
        5
      ],
      "name": "Alex Mathias Buteera"
    },
    {
      "affs": [
        1
      ],
      "name": "Abdullateef Isiaka Alagbonsi",
      "orcid": "0000-0002-5462-9950"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1jmamqyrc0anc.bib",
  "cited_by": 0,
  "doi": "10.2147/btt.s651552",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735400/",
  "id": "1jmamqyrc0anc",
  "issns": [
    "1177-5475",
    "1177-5491"
  ],
  "landing_url": "https://doi.org/10.2147/btt.s651552",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Review"
    ],
    [
      "openalex",
      "2712|Pancreatic function and diabetes"
    ]
  ],
  "openalex": "W7224769790",
  "pdf_url": "https://www.dovepress.com/article/download/121633",
  "pmcid": "PMC13735400",
  "pmid": "42991192",
  "published": "2026-10-31",
  "publisher": "Dove Press",
  "ris": "https://research.draconitic.com/paper/1jmamqyrc0anc.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:21:05Z",
      "native_id": "PMC13735400",
      "source": "pmc",
      "url": "https://doi.org/10.2147/btt.s651552"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2712|Pancreatic function and diabetes",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "TRPM7 as a Magnesium-Sensing Metabolic Checkpoint in Pancreatic β-Cell Failure and Type 2 Diabetes: From Mechanistic Insights to a Functional Biomarker Strategy",
  "title_text": "TRPM7 as a Magnesium-Sensing Metabolic Checkpoint in Pancreatic β-Cell Failure and Type 2 Diabetes: From Mechanistic Insights to a Functional Biomarker Strategy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:05Z",
  "url": "https://research.draconitic.com/paper/1jmamqyrc0anc",
  "venue": "Biologics : Targets & Therapy",
  "versions": []
}