AKT1 and Hyperglycemia: Interestingly, NTN-1 demonstrates cytoprotective capabilities in vascular endothelia, counteracting hyperglycemia-induced injury and angiogenic dysfunction through PI3K/AKT/eNOS pathway activation (Xing et al., 2017), this signaling cascade enhances eNOS enzymatic activity and protein expression, subsequently suppressing nuclear NF-κB translocation via eNOS/NO/NF-κB pathway (Yu et al., 2018).