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Effect of Tubacin on Glucose-stimulated Insulin Secretion in β Cell
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- Author:
- No author available
- Journal Title:
- JOURNAL OF RADIOIMMUNOLOGY
- Issue:
- 6
- DOI:
- 10.3969/j.issn.1008-9810.2013.06.048
- Key Word:
- 乙酰化;Tubacin;胰岛素分泌;α-微管蛋白
Abstract： 目的:观察去乙酰化酶HDAC6特异性抑制剂Tubacin对MIN6细胞胰岛素分泌的影响,并探讨其可能机制.方法:用RT-PCR检测去乙酰化酶家族成员在MIN6细胞的表达,用免疫荧光技术观察HDAC6在小鼠胰岛和MIN6细胞内的定位;分别在5.6mmol/L和25mmol/L葡萄糖的DMEM中加和不加10μmol/L Tubacin,用其处理MIN6细胞24h,收集上清,ELISA检测胰岛素浓度.同时用MTT法检测Tubacin对MIN6细胞活力的影响,RT-PCR检测上述处理条件下Insulin基因的表达情况.以Western blot和免疫荧光技术检测Tubacin 对MIN6细胞骨架蛋白α-tubulin乙酰化水平的影响.结果:MIN6细胞中各乙酰化酶家族成员mRNA的表达水平相差较大,其中HDAC6表达相对较高.HDAC6主要表达于小鼠胰岛β细胞及MIN6细胞胞浆中.在5.6mmol/L和25mmol/L葡萄糖条件下,Tubacin处理24h可以显著抑制胰岛素分泌,但不影响MIN6细胞活力.同时,在5.6mmol/L葡萄糖存在条件下Tubacin不影响胰岛素基因表达,在25mmol/L葡萄糖存在条件下Tubacin可轻度上调胰岛素基因表达.Western blot和免疫荧光结果发现,Tubacin抑制胰岛素分泌的同时伴有α-tubulin乙酰化水平增加.结论:HDAC6抑制剂Tubacin可能通过增加MIN6细胞α-tubulin乙酰化水平,改变细胞骨架的活动度而抑制胰岛素分泌.
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