T2DM is a metabolic disorder driven by insulin resistance or β-cell dysfunction, leading to vascular alterations in insulin-sensitive tissues.536 Notably, VEGF-A, primarily produced by pancreatic α and β cells, plays a key role in islet microvasculature.537 Deleting Vegf in insulin-producing cells reduces islet vascularization and impairs insulin secretion, while VEGF-A deficiency leads to islet hypoxia and elevated blood glucose levels.537–539. This evidence concerns the gene INS and metabolic disease.