INS and endothelial dysfunction: In healthy individuals this transient “spark” is hormetic, fine-tuning insulin action and vascular tone; in insulin-resistant or metabolic-syndrome phenotypes, the ROS pulse is higher and longer, synergizing with hyperglycemia and chylomicronemia to oxidize lipids/proteins, quench endothelial NO, and activate inflammasome/kinase pathways, feeding forward into endothelial dysfunction and insulin resistance (74, 75).