Work

TRPM7 as a Magnesium-Sensing Metabolic Checkpoint in Pancreatic β-Cell Failure and Type 2 Diabetes: From Mechanistic Insights to a Functional Biomarker Strategy

Year: 2026

Type: review

Abstract: Background: Traditional clinical chemistry views magnesium (Mg 2 ⁺) primarily as a homeostatic marker, with serum levels used to detect overt deficiency. However, emerging evidence indicates that intracellular Mg 2 ⁺ 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 Mg 2 ⁺-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 Mg 2 ⁺ levels. Supporting studies showed that TRPM7 regulates β-cell development and high-fat-diet-induced proliferation, while Mg 2 ⁺ 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 Mg 2 ⁺–TRPM7–mTOR signaling further links this pathway to proliferative capacity. Conclusion: TRPM7 may represent a Mg 2 ⁺-sensing metabolic checkpoint in β-cells, translating intracellular Mg 2 ⁺ availability into adaptive insulin production and compensatory proliferation. This review highlights a major translational gap in clinical chemistry, which currently relies primarily on serum Mg 2 ⁺ measurements and does not capture intracellular Mg 2 ⁺ 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. Keywords: insulin secretion, magnesium signaling, pancreatic β-cells, TRPM7, type 2 diabetes

Source: Biologics

DOI: 10.2147/btt.s651552