Metformin (400 mg/kg/d, 100 mg/kg/d, respectively) administration is associated with reduced lung endothelial hyperpermeability and systemic inflammatory response in STZ-induced diabetic mice 243 and alleviates microvascular ED by suppressing hypoxia inducible factor-1 alpha (HIF-1α)/Profilin-1 (PFN1) signaling, which mediates endothelial cell permeability during diabetic retinopathy 244. The gene discussed is PFN1; the disease is diabetic retinopathy.