Regulation of Human β-Cell Adhesion, Motility, and Insulin Secretion by Collagen IV and Its Receptor α1β1*

Collagens have been shown to influence the survival and function of cultured β-cells; however, the utilization and function of individual collagen receptors in β-cells is largely unknown. The integrin superfamily contains up to five collagen receptors, but we have determined that α1β1 is the primary receptor utilized by both fetal and adult β-cells. Cultured β-cells adhered to and migrated on collagen type IV (Col-IV), and these responses were mediated almost exclusively by α1β1. The migration of cultured β-cells to Col-IV significantly exceeded that to other matrix components suggesting that this substrate is of unique importance for β-cell motility. The interaction of α1β1 with Col-IV also resulted in significant insulin secretion at basal glucose concentrations. A subset of β-cells in developing islets was confirmed to express α1β1, and this expression co-localized with Col-IV in the basal membranes of juxtaposed endothelial cells. Our findings indicate that α1β1 and Col-IV contribute to β-cell functions known to be important for islet morphogenesis and glucose homeostasis.