Exendin-4 Protects Pancreatic Beta Cells from the Cytotoxic Effect of Rapamycin by Inhibiting JNK and p38 Phosphorylation
Exendin-4 Protects Pancreatic Beta Cells from the Cytotoxic Effect of Rapamycin by Inhibiting JNK and p38 Phosphorylation
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DOI：
10.1055/s-0030-1249035
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发表时间：
2010-05-01
影响因子：
2.2
通讯作者：
Inagaki, N.
中科院分区：
文献类型：
--
作者：
Kawasaki, Y.;Harashima, S.;Inagaki, N.
据报道，免疫抑制剂雷帕霉素降低胰腺β细胞的活力。相比之下，已发现胰高血糖素样肽-1的类似物毒蜥外泌肽-4抑制β细胞死亡并增加β细胞质量。我们研究了exendin-4对雷帕霉素在β细胞中的细胞毒性作用的影响。在鼠β细胞系MIN 6细胞和Wistar大鼠胰岛中，与10 nM雷帕霉素孵育12 h后诱导细胞死亡，但与10 nM exendin-4共孵育时未诱导细胞死亡。在MIN 6细胞和Wistar大鼠胰岛中，发现雷帕霉素在30分钟内增加c-Jun氨基末端激酶（JNK）和p38的磷酸化，而exendin-4降低它们的磷酸化。Akt和细胞外信号调节激酶（ERK）不参与exendin-4的细胞保护作用。这些结果表明，exendin-4可能通过抑制JNK和p38信号传导而对胰腺β细胞中雷帕霉素诱导的细胞死亡发挥其保护作用。
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.