Metformin Treatment Shown to Effect Citrulline Levels

Findings in human sera and patients; validated in plasma, skeletal muscle, adipose tissue of mice
Findings in human sera and patients; validated in plasma, skeletal muscle, adipose tissue of mice

HealthDay News — For patients with type 2 diabetes mellitus (T2DM), metformin treatment is associated with lower citrulline values, according to a study published online September 12 in Diabetes.

Jonathan Adam, from Helmholtz Zentrum München in Neuherberg, Germany, and colleagues used a non-targeted metabolomics approach to examine metformin's pleiotropic effect. A total of 353 metabolites were analyzed in fasting serum samples of the population-based human Cooperative Health Research in the Region of Augsburg (KORA) F4 cohort. Patients with T2DM treated with metformin (mt-T2D; 74 patients) were compared with those without antidiabetic medication (ndt-T2D; 115 patients). The initial findings were confirmed in longitudinal samples of 683 KORA participants. Findings from the human study were corroborated using murine plasma, liver, skeletal muscle, and epididymal adipose tissue samples for metformin treated-db/db mice.

The researchers found that when comparing mt-T2D with ndt-T2D, citrulline showed lower values, and an unknown metabolite X-21365 showed higher relative concentrations in human serum. In patients who started metformin treatment, citrulline was confirmed to be significantly decreased at seven years' follow-up. Significantly lower citrulline values were validated in plasma, skeletal muscle, and adipose tissue of metformin-treated mice, but not in their liver.

"In summary, we observed that serum values of citrulline were reduced under metformin treatment in human patients with T2DM and, in a translational approach, also in plasma, skeletal muscle, and epididymal adipose tissue of diabetic mice," the authors write.

Several authors disclosed financial ties to the biopharmaceutical industry.

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