PuSH - Publikationsserver des Helmholtz Zentrums München

Boulassel, S.* ; Schreier, P.C.F.* ; Melyshi, A.M.* ; Berger, J.* ; Reinach, P.S.* ; Jacob, K.* ; Boekhoff, I.* ; Breit, A.* ; Müller, T.D. ; Zierler, S.* ; Gudermann, T.* ; Khajavi, N.*

Mg2+ supplementation mitigates metabolic deficits associated with TRPM7 disruption.

J. Cell. Physiol. 240:e70042 (2025)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Transient receptor potential channel subfamily M member 7 (TRPM7) regulates cellular and systemic Mg2+ homeostasis through its channel domain and induces protein phosphorylation via its kinase domain. We recently found that mice with selective deletion of Trpm7 in β-cells develop glucose intolerance and declines in insulin secretion, primarily due to the impaired enzymatic activity of this protein. Accumulating evidence suggests that Mg2+ supplementation effectively mitigates the detrimental effects of TRPM7 disruption in various cell types. However, the impact of Mg2+ supplementation on metabolic impairments caused by TRPM7 inactivation remains unclear. In the present study, we found that Mg2+ supplementation significantly ameliorates glucose intolerance observed in high-fat-fed TRPM7 kinase-deficient mice (Trpm7R/R). However, our ex vivo analysis of islets isolated from Trpm7R/R mice revealed that Mg2+ supplementation does not enhance glucose-induced insulin secretion. Instead, the improvement appears to be partially driven by enhanced insulin sensitivity and increased β-cell proliferation. The pharmacological analysis in MIN6 cells showed that inhibiting TRPM7 with either NS8593 or VER155008 disrupts β-cell proliferation. These effects mimicked the phenotype seen in Trpm7R/R mice. We attribute this impairment to diminished ERK1/2 signaling, which suppressed PDX1 expression, while Mg2+ supplementation in vitro partially restored ERK1/2 phosphorylation levels. Collectively, Mg2+ supplementation enhances glucose metabolism in Trpm7R/R mice and mitigates the ERK1/2 signaling disruptions and proliferation arrest induced by TRPM7 inactivation in vitro. These findings provide compelling evidence that Mg2+ supplementation can reverse the adverse metabolic and cellular phenotypes associated with the loss of TRPM7 function.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Mg2+ Supplementation ; Trpm7 ; Glucose Metabolism ; Pancreatic β‐cell ; Proliferation; Insulin-secretion; Channel; Kinase; Magnesium; Proliferation; Protein
ISSN (print) / ISBN 0021-9541
e-ISSN 1097-4652
Zeitschrift Journal of Cellular Physiology
Quellenangaben Band: 240, Heft: 4, Seiten: , Artikelnummer: e70042 Supplement: ,
Verlag Wiley
Verlagsort 111 River St, Hoboken 07030-5774, Nj Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Förderungen N.K. and T.G. were supported by the Deutsche Forschungsgemeinschaft (German Research Foundation, DFG)-Project-ID 239283807-TRR-152 (P23, P15). T.D.M. received research funding from the DFG within TRR-152 (P23) and TRR-296 and the DZD.