The role of G protein-coupled receptor 40 in lipoapoptosis in mouse β-cell line NIT-1
The role of G protein-coupled receptor 40 in lipoapoptosis in mouse β-cell line NIT-1
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DOI：
10.1677/jme-06-0048
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发表时间：
2007-05-01
影响因子：
3.5
通讯作者：
Cheng, Hua
中科院分区：
文献类型：
--
作者：
Zhang, Ying;Xu, Mingtong;Cheng, Hua
游离脂肪酸（FFAs）对β细胞有不同的作用。急性暴露于FFAs刺激胰岛素分泌，而慢性暴露损害β细胞功能并诱导细胞凋亡。G蛋白偶联受体40 （GPR40）优先在p细胞中表达，并被多种FFAs激活。本研究采用小干扰RNA技术和小鼠p细胞NIT-1细胞凋亡实验，探讨GPR40在β细胞脂肪凋亡及其功能中的作用。结果表明，棕榈酸盐诱导p细胞凋亡，不通过GPR40介导，而油酸盐保护NIT-1细胞免受棕榈酸盐诱导的脂肪凋亡，至少部分通过GPR40介导。此外，通过检测磷脂酰肌醇3-激酶和MAP激酶（MAPK）通路的激活情况，我们发现油酸主要通过GPR40促进细胞外信号调节蛋白激酶MAPK通路的激活，增加早期生长反应基因-1的表达，从而对NIT-1细胞产生抗脂质凋亡作用。提示GPR40可能与p细胞质量可塑性的控制有关，GPR40可能在肥胖和2型糖尿病之间提供了联系。
Free fatty acids (FFAs) exert divergent effects on beta-cells. Acute exposure to FFAs stimulates insulin secretion, whereas chronic exposure impairs beta-cell function and induces apoptosis. The G protein-coupled receptor 40 (GPR40) is preferentially expressed in P-cells and is activated by a wide range of FFAs. In this study, we used small interfering RNA technology and apoptosis assay in mouse P-cell NIT-1 to address the role of GPR40 in beta-cell lipoapoptosis and function. Results showed that palmitate induced P-cell apoptosis, which was not mediated through GPR40, whereas oleate protected NIT-1 cells from palmitate-induced lipoapoptosis, which was mediated at least in part through GPR40. Moreover, by detecting the activation of the phosphatidylinositol 3-kinase and MAP kinase (MAPK) pathways, we found that oleate promoted the activation of extracellular signal-regulated protein kinase-MAPK pathway mainly via GPR40, increased the expression of early growth response gene-1, leading to the anti-lipoapoptotic effect on NIT-1 cells. It was suggested that GPR40 might be implicated in the control of P-cell mass plasticity and GPR40 probably provide a link between obesity and type 2 diabetes.