Vascular Destabilization and Pericyte Detachment are Mediated by hIAPP Aggregation in Transgenic Mice

<b>What is already known about this subject?:</b> - hIAPP is cytotoxic to islet endothelial cells and beta cells, and contributes to islet failure in type-2 diabetes (T2D)- hIAPP transgenic mice demonstrate islet capillary dilation, loss of vascular structures, and increased pericyte density- Impaired pericyte anchorage and vascular fragmentation drive diabetes-related vasculopathies in other tissues, like the retina, kidney, and brain<b>What is the key question?:</b> - How does the surviving microvasculature in islets respond to hIAPP deposition?<b>What are the new findings?:</b> - Endothelial cells demonstrate transcriptional downregulation of key genes involved in cytoskeleton, ECM, and cell-adhesion maintenance, including <i>Thbs1</i> , <i>Tln1</i> , and <i>Plec</i> . - Amyloid deposits disrupt homeostatic interactions between endothelial cells and pericytes.- Amyloid-adjacent islet pericytes are detached from endothelial cells and display impaired ability to modulate capillary diameter.<b>How might this impact on clinical practice in the foreseeable future?:</b> - Therapies targeting endothelial cell-pericyte interactions may restore islet microvascular stability and improve islet function, especially in the context of early T2D.