EDN1 and diabetes mellitus: To the best of our knowledge, this report is the first to investigate, in a diabetes-induced lower extremity arterial disease (LEAD) animal model: (i) femoral artery expression of three cell signalling molecules (the advanced glycation end products (AGEs), endothelin-1 (ET-1), and NOS enzymes involved in vascular pathophysiology [16,26]; (ii) femoral artery ultrastructural alterations; and (iii) metformin’s amelioration of the above mentioned parameters.