Pancreatic-Derived Factor (FAM3B), a Novel Islet Cytokine, Induces Apoptosis of Insulin-Secreting β-Cells
| Autor: | Claudia E. Robert, James F. Markmann, Ali Naji, Yuan Zhu, Matteo Trucco, Zhiyong Gao, Bryan A. Wolf, Donald H. Campbell, Weizhen Xu, Xiaopei Cao, Gang Xu, Ewan Bell, Scott Greene, Robert J. Young |
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| Rok vydání: | 2003 |
| Předmět: |
Programmed cell death
medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Apoptosis Biology Islets of Langerhans Mice Internal medicine Insulin Secretion In Situ Nick-End Labeling Tumor Cells Cultured Internal Medicine medicine Animals Humans Insulin Viability assay Annexin A5 geography geography.geographical_feature_category Dose-Response Relationship Drug Pancreatic islets Islet Rats Cell biology Pancreatic Neoplasms Cytokine medicine.anatomical_structure Endocrinology Cell culture Cytokines Insulinoma Pancreas |
| Zdroj: | Diabetes. 52:2296-2303 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/diabetes.52.9.2296 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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