Diabetes-induced hypomagnesemia is not modulated by metformin treatment in mice.

Approximately 30% of patients with type 2 diabetes mellitus (T2D) have hypomagnesemia (blood magnesium (Mg) concentration <0.7 mmol/L). In T2D patients, treatment with metformin is associated with reduced blood Mg levels. To investigate how T2D and metformin affect Mg homeostasis db/m and db/db mice were treated with metformin or placebo. Mice were housed in metabolic cages to measure food and water intake, and to collect urine and feces. Serum and urinary Mg concentrations were determined and mRNA expression of magnesiotropic genes was determined in kidney and distal colon using RT-qPCR. Db/db mice had significantly lower serum Mg levels than db/m mice. Mild hypermagnesuria was observed in the db/db mice at two weeks, but not at four weeks. Metformin-treatment had no effect on the serum Mg concentration and on the urinary Mg excretion. Both in kidney and distal colon of db/db mice, there was a compensatory upregulation in the mRNA expression of magnesiotropic genes, such as transient receptor potential melastatin 6 (Trpm6), whereas metformin treatment did not affect gene expression levels. In conclusion, we show that T2D causes hypomagnesemia and that metformin treatment has no effect on Mg homeostasis in mice.