Abnormality in Expression Levels of Gluconeogenesis-Related Genes by High-Dose Supplementation with Pyridoxamine in Mice

Pyridoxamine supplementation caused the alteration of the expression of genes encoding six gluconeogenesis-related proteins. The expression levels of phosphoenolpyruvate carboxykinase, pyruvate kinase, and pyruvate dehydrogenase kinase 4 in the pyridoxamine-supplemented mice were higher than those in the control mice. In contrast, the pyridoxamine supplementation caused lower expression levels of peroxisome proliferator-activated receptor-gamma coactivator-1alpha, carbohydrate response element-binding protein, glucocorticoid receptor, and glucose-6-phosphatase. The pyridoxamine-supplemented mice showed significantly low glucose clearance in a glucose tolerance test, but they showed no symptoms of diabetes, which was estimated according to the levels of hemoglobin A1c and blood glucose. Pyruvate challenge testing suggested that pyridoxamine supplementation enhanced gluconeogenic activity from pyruvate. The results showed that a high-dose of pyridoxamine may require a careful inquiry concerning its validity.