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

¹ Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
² Department of Pediatrics, Children’s Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
³ Expression Genomics, GlaxoSmithKline, King of Prussia, Pennsylvania
⁴ Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

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 ß-cell function, we investigated the effects of PANDER on rat, mouse, and human pancreatic islets; the ß-TC3 cell line; and the -TC cell line. PANDER protein was present in - and ß-cells of pancreatic islets, insulin-secreting ß-TC3 cells, and glucagon-secreting -TC cells. PANDER induced islet cell death in rat and human islets. Culture of ß-TC3 cells with recombinant PANDER had a dose-dependent inhibitory effect on cell viability. This effect was also time-dependent. PANDER caused apoptosis of ß-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 ß-cell apoptosis.

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