期刊
HORMONE AND METABOLIC RESEARCH
卷 42, 期 5, 页码 311-317出版社
GEORG THIEME VERLAG KG
DOI: 10.1055/s-0030-1249035
关键词
exendin-4; rapamycin; JNK; p38; beta cells
资金
- Ministry of Education, Culture, Sports, Science, and Technology, Japan
- Ministry of Health, Labor, and Welfare, Japan
- Kyoto University
- Grants-in-Aid for Scientific Research [21591132, 22590975] Funding Source: KAKEN
It has been reported that the immunosuppressant rapamycin decreases the viability of pancreatic beta cells. In contrast, exendin-4, an analogue of glucagon-like peptide-1, has been found to inhibit beta cell death and to increase beta cell mass. We investigated the effects of exendin-4 on the cytotoxic effect of rapamycin in beta cells. Incubation with 10 nM rapamycin induced cell death in 12 h in murine beta cell line MIN6 cells and Wistar rat islets, but not when coincubated with 10 nM exendin-4. Rapamycin was found to increase phosphorylation of c-Jun amino-terminal kinase (JNK) and p38 in 30 minutes in MIN6 cells and Wistar rat islets while exendin-4 decreased their phosphorylation. Akt and extracellular signal-regulated kinase (ERK) were not involved in the cytoprotective effect of exendin-4. These results indicate that exendin-4 may exert its protective effect against rapamycin-induced cell death in pancreatic beta cells by inhibiting JNK and p38 signaling.
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