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Regul Pept. 2010 Apr 9;161(1-3):43-50. doi: 10.1016/j.regpep.2009.12.017. Epub 2010 Jan 14.

Ghrelin inhibits cell apoptosis induced by lipotoxicity in pancreatic beta-cell line.

Author information

1
Department of Endocrinology, First Hospital of China Medical University, Shenyang 110001, China.

Abstract

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.

PMID:
20079380
DOI:
10.1016/j.regpep.2009.12.017
[Indexed for MEDLINE]

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