JUN and Hyperglycemia: This suggests that hyperglycemia-induced apoptosis of islet endothelium likely involves the nephrin-mediated signaling cascade, wherein phosphorylation of the tyrosine sites within the intracytoplasmic C terminal domain of nephrin activates mitogen-activated protein kinase p38 and JNK and thereby the transcription factor activating protein-1 (AP-1)/c-Jun, which modulates apoptosis.