The matricellular protein Fibulin-5 regulates β-cell proliferation in an autocrine/paracrine manner

The matricellular protein Fibulin-5 (Fbln5) is a secreted protein that is essential for elastic fiber formation, and pancreatic islets are usually surrounded by the extracellular matrix (ECM), which includes elastic fibers. However, much uncertainty remains regarding the function of the ECM and its components in β-cells. Here, we describe the role of Fbln5 in β-cell replication. Fbln5 expression was increased upon glucose stimulation in β-cells of mouse and human islets. β-Cell-specific Fbln5-knockout (βFbln5KO) mice exhibit significantly reduced β-cell proliferation in vivo but not in vitro. Secreted extracellular Fbln5 enhances β-cell replication. Fbln5-deficient β-cells exhibit the downregulated expression of the gene encoding Polo-like kinase 1 (PLK1), which is accompanied by ERK-mediated FoxM1 nuclear export. These data suggest that Fbln5 is secreted from β-cells in response to glucose and plays important roles in the appropriate maintenance of β-cell functions in an autocrine or paracrine manner.