Abstract

Background

The dysfunction of pancreatic β cells is related to the occurrence of gestational diabetes mellitus (GDM). This study aimed to investigate the mechanism underlying the effects of miR-190b on pancreatic β cell proliferation and insulin secretion.

Methods

Quantitative real-time PCR was used to detect miR-190b expression in placenta tissues from GDM patients. The effects of miR-190b on islet cells activity, proliferation, and insulin secretion were measured using MTT assay, BrdU staining, and ELISA. The relationship between miR-190b and NK6 homeobox 1 (NKX6-1) was ensured by dual luciferase reporter assay.

Results

MiR-190b was overexpressed in placenta tissues from GDM patients compared to normal pregnant woman. MiR-190b inhibitor inhibited the cell activity, proliferation, and insulin secretion of islet β cells, while miR-190b overexpression had an opposite effect. Additionally, miR-190b negatively regulated NKX6-1 expression. Overexpression of NKX6-1 reversed the inhibitory effect of miR-190b-mimics on islet β cell activity, proliferation, and insulin secretion. In mouse islets, knockdown of miR-190b promoted insulin secretion by up-regulating NKX6-1 expression.

Conclusion

Silence of miR-190b accelerated pancreatic β cell proliferation and insulin secretion via targeting NKX6-1, which might be a mechanism underlying the effects of miR-190b on the progression of GDM.

中文翻译：

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MiR-190b 通过靶向 NKX6-1 阻碍胰腺 β 细胞增殖和胰岛素分泌，并可能与妊娠糖尿病有关

摘要

背景

胰腺β细胞功能障碍与妊娠期糖尿病（GDM）的发生有关。本研究旨在探讨miR-190b对胰腺β细胞增殖和胰岛素分泌影响的潜在机制。

方法

定量实时PCR用于检测GDM患者胎盘组织中miR-190b的表达。使用 MTT 测定、BrdU 染色和 ELISA 测量 miR-190b 对胰岛细胞活性、增殖和胰岛素分泌的影响。miR-190b 和 NK6 同源框 1 (NKX6-1) 之间的关系通过双荧光素酶报告基因测定来确保。

结果

与正常孕妇相比，MiR-190b 在 GDM 患者的胎盘组织中过度表达。MiR-190b抑制剂抑制胰岛β细胞的细胞活性、增殖和胰岛素分泌，而miR-190b过表达则具有相反的作用。此外，miR-190b 负向调节 NKX6-1 的表达。NKX6-1 的过表达逆转了 miR-190b 模拟物对胰岛 β 细胞活性、增殖和胰岛素分泌的抑制作用。在小鼠胰岛中，敲除 miR-190b 通过上调 NKX6-1 表达促进胰岛素分泌。

结论

miR-190b 的沉默通过靶向 NKX6-1加速胰腺 β 细胞增殖和胰岛素分泌，这可能是 miR-190b 影响 GDM 进展的潜在机制。