Furthermore, metformin upregulates VEGF receptors (VEGFR1/R2), fatty acid binding protein 4, ERK/mitogen-activated protein kinase signaling, chemokine ligand 8, lymphocyte antigen 96, Rho kinase 1, matrix metalloproteinase 16 (MMP16) and tissue factor inhibitor-2 in human umbilical endothelial cells exposed to hyperglycemia-hypoxia [13]. This evidence concerns the gene MMP16 and Hyperglycemia.