HIF1A and Hyperglycemia: Hyperglycemia blocks HIF-1 levels and functions under hypoxia in cardiomyocytes,[68] dermal fibroblasts and endothelial cells,[64,66] retinal epithelial cells,[70] and proximal tubular cells.[65] Similar changes were also found in central nervous system, HIF-1 and its downstream VEGF were notably less in the brain of diabetic rats than in normal rats, which presented worsened neurological deficits.[71] Accumulating evidence[66,69,72–74] suggests that impaired hypoxic responses because of HIF-1 pathway dysregulation are vital pathogenic factors of diabetic complications.