Selenoprotein SelK increases the secretion of insulin from MIN6 β cells
Selenoprotein SelK increases the secretion of insulin from MIN6 β cells
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硒蛋白 SelK 增加 MIN6 β 细胞胰岛素的分泌
DOI：
10.1039/c7ra05379g
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发表时间：
2017-01-01
期刊：
影响因子：
3.9
通讯作者：
Chen, Chang-Lan
中科院分区：
文献类型：
--
作者：
Meng, Xue-Lian;Zhang, Hui-Ling;Chen, Chang-Lan
微量元素硒对人类和动物具有胰岛素样作用。本研究探讨了小鼠硒蛋白K（mSelK）对小鼠MIN 6 β细胞分泌胰岛素的影响及其机制。使用腺病毒载体Ad-mSelK在MIN 6 β细胞中过表达mSelK基因。同样，慢病毒载体LV-mSelK-RNAi用于敲低MIN 6 B细胞中的mSelK表达。结果表明，过表达/敲低mSelK可增加/减少MIN 6 β细胞的胰岛素分泌。同时，胞浆游离Ca 2+水平和三磷酸肌醇受体3型（IP 3R 3）的表达也增加/减少作为过度表达/敲低mSelK在MIN 6 β细胞中的结果。过表达/敲低mSelK不影响MIN 6 β细胞中谷胱甘肽过氧化物酶1（GPx 1）的表达。进一步的研究表明，用硒补充剂（亚硒酸钠，Na 2SeO 3）处理MIN 6 β细胞显著增加mSelK表达和胰岛素释放水平。此外，通过添加葡萄糖，MIN 6 β细胞中的mSelK蛋白水平也显著上调。这些结果表明，mSelK在微量元素硒促进MIN 6 β细胞分泌胰岛素的过程中起着重要作用。mSelK的表达可能通过增加内质网（endoplasmic reticulum，ER）上IP 3R 3的表达而增加胰岛素的分泌，IP 3R 3的表达通过促进ER释放Ca ~（2+）而提高胞浆游离Ca ~（2+）水平。
The trace element selenium has an insulin-like effect on humans and animals. In this study, the effect and mechanism of mouse selenoprotein K (mSelK) on the secretion of insulin from mouse MIN6 beta cells were investigated. An adenovirus vector, Ad-mSelK, was used to over-express the mSelK gene in the MIN6 beta cells. Likewise, a lentivirus vector, LV-mSelK-RNAi, was used to knockdown mSelK expression in the MIN6 b cells. It was shown that the over-expression/knockdown of mSelK could increase/decrease the insulin secretion from MIN6 beta cells. Meanwhile, the cytosolic free Ca2+ level and inositol trisphosphate receptor type 3 (IP3R3) expression were also increased/decreased significantly as a consequence of the over-expression/knockdown of mSelK in MIN6 beta cells. Over-expression/knockdown of mSelK did not affect the expression of glutathione peroxidase 1 (GPx1) in the MIN6 beta cells. Further studies revealed that the mSelK expression and insulin release levels were increased significantly by treatment of MIN6 beta cells with selenium supplement (sodium selenite, Na2SeO3). In addition, mSelK protein levels were also up-regulated significantly in MIN6 beta cells by adding glucose. These results suggest that mSelK plays a vital role in the process of trace element selenium promoting the secretion of insulin from MIN6 beta cells. The expression of mSelK may increase the secretion of insulin by improving the expression of IP3R3 on the endoplasmic reticulum (ER), which elevated the cytosolic free Ca2+ level by enhancing the release of Ca2+ from the ER.