scholarly journals Baseline gut microbiome composition predicts metformin therapy short-term efficacy in newly diagnosed type 2 diabetes patients

PLoS ONE ◽  
2020 ◽  
Vol 15 (10) ◽  
pp. e0241338
Author(s):  
Ilze Elbere ◽  
Ivars Silamikelis ◽  
Ilze Izabella Dindune ◽  
Ineta Kalnina ◽  
Monta Ustinova ◽  
...  
2020 ◽  
Vol 98 (6) ◽  
pp. 400-411 ◽  
Author(s):  
Hacene Bouras ◽  
Sara R. Roig ◽  
Steef Kurstjens ◽  
Cees J.J. Tack ◽  
Mohamed Kebieche ◽  
...  

Metformin therapy is associated with lower serum magnesium (Mg2+) levels in type 2 diabetes patients. The TRPM6 channel determines the fine-tuning of Mg2+ (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 Mg2+ absorption, 25Mg2+ 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 25Mg2+ 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 Mg2+ concentrations and fractional excretion of Mg2+. 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 Mg2+ concentration in type 2 diabetes patients.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1040-P
Author(s):  
EMMA WOKS ◽  
MARTINE CLAUDE ETOA NDZIE ETOGA ◽  
RAICHA NAMBA ◽  
JEAN CLAUDE NJABOU KATTE ◽  
JEAN CLAUDE MBANYA ◽  
...  

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