Candidate plasticity gene 16 mediates suppression of insulin gene expression in rat insulinoma INS-1 cells under glucotoxic conditions.
Candidate plasticity gene 16 mediates suppression of insulin gene expression in rat insulinoma INS-1 cells under glucotoxic conditions.
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候选可塑性基因 16 在糖毒性条件下介导大鼠胰岛素瘤 INS-1 细胞中胰岛素基因表达的抑制。
DOI：
10.1016/j.bbrc.2019.03.036
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Sugiyama Y.
中科院分区：
文献类型：
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作者：
Nakane T;Ido A;Higuchi T;Todaka H;Morisawa K;Nagamine T;Fukunaga K;Sakamoto S;Murao K;Sugiyama Y.
慢性高血糖导致胰腺β细胞功能障碍，胰岛素分泌受损和胰岛素基因表达抑制，称为糖毒性。胰岛素基因的表达受多种蛋白激酶和蛋白磷酸酶的调控。然而，糖毒性中胰岛素基因表达抑制的分子机制尚不完全清楚。在这项研究中，我们使用大鼠胰岛素瘤INS-1 细胞作为胰腺糖毒性模型。在INS-1 细胞中，胰岛素基因表达在11.2 mM葡萄糖培养7天后上调，在22.4 mM葡萄糖培养7天后下调。为了确定参与胰岛素基因表达抑制的蛋白激酶和蛋白磷酸酶，我们使用微阵列分析和实时PCR分析了在11.2 mM或22.4 mM葡萄糖培养7天的INS-1 细胞中的基因表达。九种蛋白激酶的表达水平受到糖中毒条件的影响。特别是在这些条件下，INS-1 细胞中CPG16的表达水平升高。转染CPG16会降低胰岛素启动子活性，而激酶死亡突变体CPG16则不会影响胰岛素启动子活性。这些结果表明，CPG16在糖中毒条件下抑制胰腺β-细胞胰岛素基因表达中发挥作用。
Chronic hyperglycemia causes pancreatic β-cell dysfunction, impaired insulin secretion and suppression of insulin gene expression, referred to as glucotoxicity. Insulin gene expression is regulated by several protein kinases and protein phosphatases. However, the molecular mechanisms of the suppressed insulin gene expression in glucotoxicity are not fully understood. In this study, we employed rat insulinoma INS-1 cells as a model of pancreatic glucotoxicity. In INS-1 cells, insulin gene expression is up-regulated by incubation with 11.2 mM glucose for 7 days and down-regulated by incubation with 22.4 mM glucose for the same period. To identify the protein kinases and protein phosphatases involved in the suppression of insulin gene expression, we analyzed gene expression in INS-1 cells cultured with 11.2 mM or 22.4 mM glucose for 7 days using microarray analysis and real-time PCR. The expression levels of nine protein kinases were affected by glucotoxic conditions. In particular, CPG16 expression level was increased in INS-1 cells under these conditions. Transfection of CPG16 decreased insulin promoter activity, whereas kinase-dead mutant of CPG16 did not affect this. These results suggest that CPG16 plays a role in the suppression of insulin gene expression in pancreatic β-cells under glucotoxic conditions.