Ghrelin inhibits cell apoptosis induced by lipotoxicity in pancreatic beta-cell line.
Lipotoxicity plays an important role in underlying mechanism of type 2 diabetes. Prolonged exposure of pancreatic beta-cells to elevated levels of fatty acid is associated with beta-cell apoptosis. Ghrelin is a 28-amino acid peptide, mainly secreted from X/A like cells of gastric fungus. The effects of ghrelin are considered to be broadly including cell protection. However, the mechanism of ghrelin protecting pancreatic beta-cells against lipotoxicity is unknown. Our study showed that ghrelin promoted cell survival and attenuated palmitate-induced apoptosis in pancreatic beta-cells (MIN6). Exposure of MIN6 cells to palmitate (0.4mM) for 24h caused a significant increase in cell apoptosis, which could be protected by ghrelin. Exposure of MIN6 cells to ghrelin caused a rapid activation of protein kinase B (PKB) and inhibition of c-Jun N-terminal kinase (JNK) under lipotoxic state. Furthermore, LY294002, a PI3K inhibitor, abolished the anti-lipotoxic effect of ghrelin, as well as ghrelin-induced inhibition of JNK, while JNK inhibitor, SP600125 enhanced protective effect of ghrelin on MIN6 cells. Ghrelin also inhibited the mitochondrial pathway of apoptosis and it down-regulated Bax in MIN6 cells. For secretion experiment, ghrelin suppressed insulin release under palmitate-incubated state. Our findings suggest that ghrelin may prevent lipotoxicity-induced apoptosis in MIN6 cells through activation of PKB, inhibition of JNK and mitochondrial pathway.
Wang
Wei
W
Department of Endocrinology, First Hospital of China Medical University, Shenyang 110001, China.
Zhang
Dan
D
Zhao
Hong
H
Chen
Ying
Y
Liu
Ying
Y
Cao
Cuiping
C
Han
Lingling
L
Liu
Guoliang
G
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D054439:Ghrelin / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D019308:Palmitic Acid / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D000873:Anthracenes; D054439:Ghrelin; C432165:pyrazolanthrone; D019308:Palmitic Acid; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3