Suppression of the nuclear factor Eny2 increases insulin secretion in poorly functioning INS-1E insulinoma cells.

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-05-10 DOI:10.1155/2012/460869
P Dames, M Weise, R Puff, B Göke, K G Parhofer, J Seissler, A Lechner
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引用次数: 5

Abstract

Eny2, the mammalian ortholog of yeast Sus1 and drosophila E(y)2, is a nuclear factor that participates in several steps of gene transcription and in mRNA export. We had previously found that Eny2 expression changes in mouse pancreatic islets during the metabolic adaptation to pregnancy. We therefore hypothesized that the protein contributes to the regulation of islet endocrine cell function and tested this hypothesis in rat INS-1E insulinoma cells. Overexpression of Eny2 had no effect but siRNA-mediated knockdown of Eny2 resulted in markedly increased glucose and exendin-4-induced insulin secretion from otherwise poorly glucose-responsive INS-1E cells. Insulin content, cellular viability, and the expression levels of several key components of glucose sensing remained unchanged; however glucose-dependent cellular metabolism was higher after Eny2 knockdown. Suppression of Eny2 enhanced the intracellular incretin signal downstream of cAMP. The use of specific cAMP analogues and pathway inhibitors primarily implicated the PKA and to a lesser extent the EPAC pathway. In summary, we identified a potential link between the nuclear protein Eny2 and insulin secretion. Suppression of Eny2 resulted in increased glucose and incretin-induced insulin release from a poorly glucose-responsive INS-1E subline. Whether these findings extend to other experimental conditions or to in vivo physiology needs to be determined in further studies.

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抑制核因子Eny2可增加功能不良的INS-1E胰岛素瘤细胞的胰岛素分泌。
Eny2是酵母Sus1和果蝇E(y)2的哺乳动物同源基因,是参与基因转录和mRNA输出的几个步骤的核因子。我们之前已经发现小鼠胰岛在妊娠代谢适应过程中Eny2的表达发生了变化。因此,我们假设该蛋白参与了胰岛内分泌细胞功能的调节,并在大鼠INS-1E胰岛素瘤细胞中验证了这一假设。Eny2的过表达没有影响,但sirna介导的Eny2敲低导致葡萄糖和exendin-4诱导的胰岛素分泌明显增加,否则葡萄糖反应较差的INS-1E细胞。胰岛素含量、细胞活力和葡萄糖感知的几个关键成分的表达水平保持不变;然而,敲除Eny2后,葡萄糖依赖型细胞代谢更高。Eny2的抑制增强了cAMP下游的细胞内肠促胰岛素信号。特异性cAMP类似物和途径抑制剂的使用主要涉及PKA和较小程度的EPAC途径。总之,我们发现了核蛋白Eny2和胰岛素分泌之间的潜在联系。抑制Eny2导致葡萄糖增加和肠促胰岛素诱导的胰岛素从葡萄糖反应不良的INS-1E亚群中释放。这些发现是否适用于其他实验条件或体内生理需要在进一步的研究中确定。
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来源期刊
Experimental Diabetes Research
Experimental Diabetes Research 医学-内分泌学与代谢
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