Local Integrin Activation in Pancreatic Cells Targets Insulin Secretion to the Vasculature

The extracellular matrix (ECM) in the islets of Langerhans critically affects s cell functions via integrin activation. But, whether these ECM actions depend on driving the spatial organisation of the s cells, as they do in epithelial cells, is unknown. Here, we show that in situ, within islets of Langerhans, focal adhesion activation in s cells occurs exclusively where they contact the capillary ECM (vascular face). In cultured s cells, 3D mapping shows enriched insulin granule fusion where the cells contact ECM proteins. Targeting depends on s1 integrin receptors and focal adhesion kinase. Cell culture on micro-contact printed stripes of Ecadherin and fibronectin shows s cell contact at the fibronectin stripe selectively activates focal adhesions, enriches exocytic machinery and insulin granule fusion. We conclude integrin activation does orientate s cells and target insulin secretion to the islet capillaries. This might be important for islet function and may change in disease.