TRPM7 as a Magnesium-Sensing Metabolic Checkpoint in Pancreatic β-Cell Failure and Type 2 Diabetes: From Mechanistic Insights to a Functional Biomarker Strategy
6 affiliations
- 1Department of Biochemistry, Adventist University of Central Africa (AUCA); Adventist School of Medicine of East Central Africa (ASOME), Kigali, Rwanda
- 2Department of Physiology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Huye, Rwanda
- 3Department of Microbiology, Adventist University of Central Africa (AUCA); Adventist School of Medicine of East Central Africa (ASOME), Kigali, Rwanda
- 4Department of Intensive Care Unit, Centre Hospitalier Universitaire de Kigali / University Teaching Hospital of Kigali (CHUK), Kigali, Rwanda
- 5Vice Dean, Adventist School of Medicine of East-Central Africa (ASOME), Kigali, Rwanda
- 6Associate Dean of Medical Education, Adventist School of Medicine of East-Central Africa (ASOME), Kigali, Rwanda
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).
Methods: 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.
Results: 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.
Conclusion: 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.
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BibTeX
@article{kampire2026trpm7,
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}},
author = {Marie Gorette Kampire and Jean Claude Hakizimana and Joseph Mucumbitsi and Callixta Kaneza and Bushobozi Themistocles and Sophie Mukantwari and Jean Mfizi Ngaboyishema and Alex Mathias Buteera and Abdullateef Isiaka Alagbonsi},
journal = {Biologics : Targets \& Therapy},
year = {2026},
month = oct,
doi = {10.2147/btt.s651552},
url = {https://doi.org/10.2147/btt.s651552},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - TRPM7 as a Magnesium-Sensing Metabolic Checkpoint in Pancreatic β-Cell Failure and Type 2 Diabetes: From Mechanistic Insights to a Functional Biomarker Strategy
AU - Marie Gorette Kampire
AU - Jean Claude Hakizimana
AU - Joseph Mucumbitsi
AU - Callixta Kaneza
AU - Bushobozi Themistocles
AU - Sophie Mukantwari
AU - Jean Mfizi Ngaboyishema
AU - Alex Mathias Buteera
AU - Abdullateef Isiaka Alagbonsi
PY - 2026
DA - 2026/10/31
JO - Biologics : Targets & Therapy
DO - 10.2147/btt.s651552
UR - https://doi.org/10.2147/btt.s651552
AB - 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). Methods: 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. Results: 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. Conclusion: 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.
SN - 1177-5475
SN - 1177-5491
ER -