title: Pancreatic-derived factor (FAM3B), a novel islet cytokine, induces apoptosis of insulin-secreting beta-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 beta-cell function, we investigated the effects of PANDER on rat, mouse, and human pancreatic islets; the beta-TC3 cell line; and the alpha-TC cell line. PANDER protein was present in alpha- and beta-cells of pancreatic islets, insulin-secreting beta-TC3 cells, and glucagon-secreting alpha-TC cells. PANDER induced islet cell death in rat and human islets. Culture of beta-TC3 cells with recombinant PANDER had a dose-dependent inhibitory effect on cell viability. This effect was also time-dependent. PANDER caused apoptosis of beta-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 Ca(2+) levels or nitric oxide levels. However, PANDER activated caspase-3. Hence, PANDER may have a role in the process of pancreatic beta-cell apoptosis.
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, 19104, USA.
authors.forename: Xiaopei
authors.initials: X
authors.lastname: Cao
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Gao
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Robert
authors.forename: Scott
authors.initials: S
authors.lastname: Greene
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.forename: Weizhen
authors.initials: W
authors.lastname: Xu
authors.forename: Ewan
authors.initials: E
authors.lastname: Bell
authors.forename: Don
authors.initials: D
authors.lastname: Campbell
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Robert
authors.initials: R
authors.lastname: Young
authors.forename: Matteo
authors.initials: M
authors.lastname: Trucco
authors.forename: James F
authors.initials: JF
authors.lastname: Markmann
authors.forename: Ali
authors.initials: A
authors.lastname: Naji
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Wolf
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects*; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007340:Insulinoma; D007515:Islets of Langerhans / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D010190:Pancreatic Neoplasms; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D017304:Annexin A5; D016207:Cytokines; D007328:Insulin