Metformin regulates TRPM6, a potential explanation for magnesium imbalance in type 2 diabetes patients

Bouras, Hacene and Roig, Sara R. and Kurstjens, Steef and Tack, Cees J. J. and Kebieche, Mohamed and de Baaij, Jeroen H. F. and Hoenderop, Joost G. J.. (2020) Metformin regulates TRPM6, a potential explanation for magnesium imbalance in type 2 diabetes patients. Canadian journal of physiology and pharmacology, 98 (6). pp. 400-411.

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Official URL: https://edoc.unibas.ch/86670/

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Metformin therapy is associated with lower serum magnesium (Mg; 2+; ) levels in type 2 diabetes patients. The TRPM6 channel determines the fine-tuning of Mg; 2+; (re)absorption in intestine and kidney. Therefore, we aimed to investigate the short- and long-term effects of metformin on TRPM6. Patch clamp recordings and biotinylation assays were performed upon 1 h of incubation with metformin in TRPM6-transfected HEK293 cells. Additionally, 24 h of treatment of mDCT15 kidney and hCaco-2 colon cells with metformin was applied to measure the effects on endogenous; TRPM6; expression by quantitative real-time PCR. To assess Mg; 2+; absorption,; 25; Mg; 2+; uptake measurements were performed using inductively coupled plasma mass spectrometry. Short-term effects of metformin significantly increased TRPM6 activity and its cell surface trafficking. In contrast, long-term effects significantly decreased; TRPM6; mRNA expression and; 25; Mg; 2+; uptake. Metformin lowered; TRPM6; mRNA levels independently of insulin- and AMPK-mediated pathways. Moreover, in type 2 diabetes patients, metformin therapy was associated with lower plasma Mg; 2+; concentrations and fractional excretion of Mg; 2+; . Thereby, short-term metformin treatment increases TRPM6 activity explained by enhanced cell surface expression. Conversely, long-term metformin treatment results in downregulation of; TRPM6; gene expression in intestine and kidney cells. This long-term effect translated in an inverse correlation between metformin and plasma Mg; 2+; concentration in type 2 diabetes patients.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Imaging Core Facility (Biehlmaier)
UniBasel Contributors:Roig Merino, Sara Raquel
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:03 Mar 2022 14:57
Deposited On:03 Mar 2022 14:57

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