title: Effect of PANDER in βTC6-cell lipoapoptosis and the protective role of exendin-4.
abstract: Chronic exposure to high concentrations of saturated fatty acids, such as palmitic acid (PA), leads to apoptosis of pancreatic β-cells through the activation of the c-Jun N-terminal kinase (JNK) signaling pathway. This study of β-cell lipoapoptosis was designed to investigate the roles of pancreatic-derived factor (PANDER), a pro-apoptosis cytokine-like peptide, and exendin-4, a long-acting agonist of the hormone glucagon-like peptide-1 (GLP-1) receptor and anti-apoptosis factor. The glucose-sensitive mouse β-pancreatic cell line, βTC6, was used to investigate the mechanisms of PA-induced apoptosis. Twenty-four hours of PA exposure led to increased PANDER expression in a dose- and time-dependent manner, and significantly increased phosphorylation of JNK. Treatment with the JNK-specific inhibitor SP600125 reduced the PA-induced PANDER expression. After the 24h of PA exposure, cells also underwent marked apoptosis and showed increased activation of the apoptosis protease, caspase-3. The small interfering (si)RNA-mediated silencing of PANDER gene expression significantly reduced both of these effects. When PA-treated βTC6 cells were exposed to exogenous exendin-4, JNK activation was inhibited, PANDER expression was decreased, and the numbers of apoptotic cells were reduced. Collectively, these results demonstrated that the JNK-mediated signaling mechanism of PA-induced β-cell apoptosis involves up-regulated expression of PANDER and activation of caspase-3. Exendin-4 may protect against lipoapoptosis by interfering with the JNK-PANDER pathway.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China.
authors.forename: Jing-Nan
authors.initials: JN
authors.lastname: Xiang
authors.forename: Dan-Ling
authors.initials: DL
authors.lastname: Chen
authors.forename: Li-Yong
authors.initials: LY
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D019610:Cytoprotection; D000077270:Exenatide; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D019308:Palmitic Acid / Q000378:metabolism* / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D014688:Venoms / Q000494:pharmacology*
chemical_list: D016207:Cytokines; C504749:PANDER protein, mouse; D010455:Peptides; D014688:Venoms; D019308:Palmitic Acid; D000077270:Exenatide; D048670:MAP Kinase Kinase 4