title: Exendin-4, a glucagon-like peptide-1 receptor agonist, inhibits cell apoptosis induced by lipotoxicity in pancreatic β-cell line.
abstract: Lipotoxicity plays an important role in the underlying mechanism of type 2 diabetes mellitus. Prolonged exposure of pancreatic β-cells to elevated concentrations of fatty acid is associated with β-cell apoptosis. Recently, glucagon-like peptide-1 (GLP-1) receptor agonists have been reported to have direct beneficial effects on β-cells, such as anti-apoptotic effects, increased β-cell mass, and improvement of β-cell function. The mechanism of GLP-1 receptor agonists' protection of pancreatic β-cells against lipotoxicity is not completely understood. We investigated whether the GLP-1 receptor agonist exendin-4 promoted cell survival and attenuated palmitate-induced apoptosis in murine pancreatic β-cells (MIN6). Exposure of MIN6 cells to palmitate (0.4mM) for 24h caused a significant increase in cell apoptosis, which was inhibited by exendin-4. Exposure of MIN6 cells to exendin-4 caused rapid activation of protein kinase B (PKB) under lipotoxic conditions. Furthermore, LY294002, a PI3K inhibitor, abolished the anti-lipotoxic effect of exendin-4 on MIN6 cells. Exendin-4 also inhibited the mitochondrial pathway of apoptosis and down-regulated Bax in MIN6 cells. Exendin-4 enhanced glucose-stimulated insulin secretion in the presence of palmitate. Our findings suggest that exendin-4 may prevent lipotoxicity-induced apoptosis in MIN6 cells through activation of PKB and inhibition of the mitochondrial pathway.
authors: Department of Endocrinology, The First Affiliated Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang, Liaoning 110001, China. weiqianinsy@gmail.com
authors: Qian
authors: Q
authors: Wei
authors: Yu Qiang
authors: YQ
authors: Sun
authors: Jin
authors: J
authors: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010168:Palmitates / Q000633:toxicity*; D010455:Peptides / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018027:Receptors, Glucagon / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction; D014688:Venoms / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D010168:Palmitates; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D018027:Receptors, Glucagon; D014688:Venoms; D051028:bcl-2-Associated X Protein; D000077270:Exenatide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt