Extracellular Matrix Protects Pancreatic Beta-Cells Against Apoptosis: Role of Short- and Long-Term Signaling Pathways

Beta-cells cultured on laminin-332 rich surfaces improve their functions. This study provides evidence for the activation of signaling pathways and gene expression by laminin-332 leading to improved beta-cell survival. Laminin-332 protect sorted rat beta-cells against apoptosis under standard conditions (11.2 mmol/l glucose, 10% serum), after serum deprivation (1% serum), and in response to interleukin-1 (IL-1; 2 ng/ml), compared with the poly-L-lysine control. Caspase-8 activity was reduced in cells cultured on laminin-332, whereas FAK, Akt and ERK phosphorylation was augmented. Treatment with an anti-1 integrin antibody, with the ERK pathway inhibitor PD98059, and/or with the phosphatidylinositol 3-kinase inhibitor LY294002 augmented cell death on the laminin-332 rich matrix but not on pLL.