Pancreatic-Derived Factor (FAM3B), a Novel Islet Cytokine, Induces Apoptosis of Insulin-Secreting β-Cells

Abstract

PANDER (PANcreatic DERived factor, FAM3B), a newly discovered secreted cytokine, is specifically expressed at high levels in the islets of Langerhans of the endocrine pancreas. To evaluate the role of PANDER in β-cell function, we investigated the effects of PANDER on rat, mouse, and human pancreatic islets; the β-TC3 cell line; and the α-TC cell line. PANDER protein was present in α- and β-cells of pancreatic islets, insulin-secreting β-TC3 cells, and glucagon-secreting α-TC cells. PANDER induced islet cell death in rat and human islets. Culture of β-TC3 cells with recombinant PANDER had a dose-dependent inhibitory effect on cell viability. This effect was also time-dependent. PANDER caused apoptosis of β-cells as assessed by electron microscopy, annexin V fluorescent staining, and flow-cytometric terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. PANDER did not affect cytosolic Ca²⁺ levels or nitric oxide levels. However, PANDER activated caspase-3. Hence, PANDER may have a role in the process of pancreatic β-cell apoptosis.