Fig. 8: Summary of DMF effects on energetic EC metabolism.

The results of this work show how DMF induces glucose uptake through upregulation of GLUT1 expression. This increase in glucose uptake leads to a greater glycolytic rate and lactate secretion to the extracellular media. Conversely, glutamine uptake is diminished in cells treated with DMF, and its oxidation through the TCA cycle is reduced. DMF diminished PHGDH activity and synthesis of serine and glycine from glucose. It is described in the bibliography that DMF inhibits VEGFR2 expression, and that extracellular glycine has been seen to promote VEGF signaling and angiogenesis through upregulation of mitochondrial activity. Whether inhibition of glycine metabolism is related with the anti-angiogenic activity of DMF remains unclear.