Visfatin inhibits apoptosis of pancreatic β-cell line, MIN6, via the mitogen-activated protein kinase/phosphoinositide 3-kinase pathway
Visfatin inhibits apoptosis of pancreatic β-cell line, MIN6, via the mitogen-activated protein kinase/phosphoinositide 3-kinase pathway
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DOI：
10.1530/jme-10-0106
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发表时间：
2011-08-01
影响因子：
3.5
通讯作者：
Peng, Yongde
中科院分区：
文献类型：
--
作者：
Cheng, Qun;Dong, Weipin;Peng, Yongde
内脂素是一种脂肪细胞因子，通过与胰岛素受体结合在减轻胰岛素抵抗中发挥重要作用。内脂素在细胞凋亡和炎症的调节中起着重要作用，其作用机制尚不清楚。本研究探讨了内脂素对棕榈酸诱导的小鼠胰岛β细胞株MIN 6凋亡的保护作用。用棕榈酸酯和/或重组内脂素处理细胞。采用1-（4，5-二甲基噻唑-2-基）-3，5-二苯基甲瓒法检测细胞增殖，V-FITC/碘化丙啶染色检测细胞凋亡和坏死，Western blot检测促凋亡蛋白的表达。与内脂素孵育的细胞的细胞增殖的浓度依赖性增加（10（-7）M和24小时相比，1.55倍，P < 0.05）。内脂素显着减少棕榈酸酯诱导的细胞凋亡，并引起几个促凋亡蛋白的表达，包括Bcl-2的上调和细胞色素c和caspase 3的显着下调的显着变化。Visfatin还以时间和浓度依赖性方式激活ERK 1/2和磷酸肌醇3-激酶（PI 3 K）/AKT信号通路，并且visfatin对细胞凋亡的影响可被特异性ERK 1/2和PI 3 K/AKT抑制剂PD 098059和LY 294002阻断。我们的结论是内脂素可以增加β细胞增殖和防止凋亡，激活细胞内信号，并调节促凋亡蛋白的表达。内脂素的抗凋亡作用是通过激活丝裂原活化蛋白激酶依赖性和PI 3 K依赖性信号通路介导的。
Visfatin is an adipocytokine that plays an important role in attenuating insulin resistance by binding to insulin receptor. It has been suggested that visfatin plays a role in the regulation of cell apoptosis and inflammation by an as yet unidentified mechanism. This study investigated the protective effects of visfatin on palmitate-induced islet beta-cell apoptosis in the clonal mouse pancreatic beta-cell line MIN6. The cells were treated with palmitate and/or recombinant visfatin. An 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan assay was used to detect cell proliferation, V-FITC/propidium iodide staining was used to measure cell apoptosis and necrosis, and western blot analysis was used to detect the expression of proapoptotic proteins. The incubation of the cells with visfatin led to a concentration-dependent increase of cell proliferation (1.55-fold at 10(-7) M and 24 h compared with control, P < 0.05). Visfatin significantly reduced the cell apoptosis induced by palmitate and caused a significant change in the expression of several proapoptotic proteins, including upregulation of Bcl-2 and a marked downregulation of cytochrome c and caspase 3. Visfatin also activated the ERK1/2 and the phosphoinositide 3-kinase (PI3K)/AKT signaling pathways in a time-and concentration-dependent manner, and the effect of visfatin on apoptosis was blocked by the specific ERK1/2 and PI3K/AKT inhibitors, PD098059 and LY294002. We conclude that visfatin can increase beta-cell proliferation and prevent apoptosis, activate intracellular signaling, and regulate the expression of proapoptotic proteins. The antiapoptotic action of visfatin is mediated by activation of mitogen-activated protein kinase-dependent and PI3K-dependent signaling pathways.