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The efficiency of insulin production and its content in insulin-expressing model β-cells correlate with their Zn2+ levels
Open Biology ( IF 5.8 ) Pub Date : 2020-10-21 , DOI: 10.1098/rsob.200137
Petra Dzianová 1 , Seiya Asai 1, 2 , Martina Chrudinová 1 , Lucie Kosinová 3 , Pavlo Potalitsyn 1, 2 , Pavel Šácha 1 , Romana Hadravová 1 , Irena Selicharová 1 , Jan Kříž 3 , Johan P Turkenburg 4 , Andrzej Marek Brzozowski 4 , Jiří Jiráček 1 , Lenka Žáková 1
Affiliation  

Insulin is produced and stored inside the pancreatic β-cell secretory granules, where it is assumed to form Zn2+-stabilized oligomers. However, the actual storage forms of this hormone and the impact of zinc ions on insulin production in vivo are not known. Our initial X-ray fluorescence experiment on granules from native Langerhans islets and insulinoma-derived INS-1E cells revealed a considerable difference in the zinc content. This led our further investigation to evaluate the impact of the intra-granular Zn2+ levels on the production and storage of insulin in different model β-cells. Here, we systematically compared zinc and insulin contents in the permanent INS-1E and BRIN-BD11 β-cells and in the native rat pancreatic islets by flow cytometry, confocal microscopy, immunoblotting, specific messenger RNA (mRNA) and total insulin analysis. These studies revealed an impaired insulin production in the permanent β-cell lines with the diminished intracellular zinc content. The drop in insulin and Zn2+ levels was paralleled by a lower expression of ZnT8 zinc transporter mRNA and hampered proinsulin processing/folding in both permanent cell lines. To summarize, we showed that the disruption of zinc homeostasis in the model β-cells correlated with their impaired insulin and ZnT8 production. This indicates a need for in-depth fundamental research about the role of zinc in insulin production and storage.



中文翻译:

胰岛素表达模型 β 细胞的胰岛素产生效率及其含量与其 Zn2+ 水平相关

胰岛素在胰腺 β 细胞分泌颗粒内产生并储存,假定在其中形成 Zn 2+稳定的寡聚物。然而,这种激素的实际储存形式以及锌离子对体内胰岛素产生的影响尚不清楚。我们对天然朗格汉斯胰岛和胰岛素瘤衍生的 INS-1E 细胞的颗粒进行的初步 X 射线荧光实验显示,锌含量存在显着差异。这促使我们进一步研究评估颗粒内 Zn 2+水平对不同模型 β 细胞中胰岛素产生和储存的影响。在这里,我们通过流式细胞术、共聚焦显微镜、免疫印迹、特异性信使 RNA (mRNA) 和总胰岛素分析,系统比较了永久 INS-1E 和 BRIN-BD11 β 细胞以及天然大鼠胰岛中的锌和胰岛素含量。这些研究表明,随着细胞内锌含量的减少,永久β细胞系中的胰岛素产生受损。胰岛素和 Zn 2+水平的下降与ZnT8 锌转运蛋白 mRNA 表达的降低同时发生,并阻碍了两种永久细胞系中胰岛素原的加工/折叠。总而言之,我们发现模型 β 细胞中锌稳态的破坏与其胰岛素和 ZnT8 产生受损相关。这表明需要对锌在胰岛素产生和储存中的作用进行深入的基础研究。

更新日期:2020-10-30
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