The Vascular Basement Membrane: A Niche for Insulin Gene Expression and β Cell Proliferation

SummaryEndocrine pancreatic β cells require endothelial signals for their differentiation and function. However, the molecular basis for such signals remains unknown. Here, we show that β cells, in contrast to the exocrine pancreatic cells, do not form a basement membrane. Instead, by using VEGF-A, they attract endothelial cells, which form capillaries with a vascular basement membrane next to the β cells. We have identified laminins, among other vascular basement membrane proteins, as endothelial signals, which promote insulin gene expression and proliferation in β cells. We further demonstrate that β1-integrin is required for the β cell response to the laminins. The proposed mechanism explains why β cells must interact with endothelial cells, and it may apply to other cellular processes in which endothelial signals are required.