Blockade of 1 Integrin–Laminin-5 Interaction Affects Spreading and Insulin Secretion of Rat Beta-Cells Attached on Extracellular Matrix

In this study, the authors show that outside-in signaling via engagement of B1 integrins by laminin-332 is an important component of normal B-cell function. By using specific blocking antibodies, the authors demonstrated that laminin-332 is the component present in 804G matrix (rat bladder carcinoma cell line), responsible for the effect of 804G matrix on B-cell function and spreading. Only the B1 integrin was detected in B-cells, a well-known laminin-332 ligand. Anti–B1 integrin antibody reduced the spreading of B-cells on 804G matrix. The blockade of the interaction between B1 integrins and laminin-332 resulted in a reduction in glucose-stimulated insulin secretion. Blocking anti–B1 integrin antibody also inhibited focal adhesion kinase phosphorylation induced by 804G matrix. In conclusion, anti–B1 integrin and –laminin-332 antibodies interfere with the spreading of B-cells, resulting in decreased insulin secretion in response to glucose.