MiR-190b impedes pancreatic β cell proliferation and insulin secretion by targeting NKX6-1 and may associate to gestational diabetes mellitus

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.

Keywords:

• Gestational diabetes mellitus
• islet β cell
• miR-190b
• NKX6-1
• insulin secretion

Disclosure statement

The authors state that there are no conflicts of interest to disclose.

Author contributions

SW and DW designed the study, supervised the data collection, analyzed the data, XS interpreted the data and prepare the manuscript for publication, YL, DL and BC supervised the data collection, analyzed the data and reviewed the draft of the manuscript. All authors have read and approved the manuscript.

Data availability statement

All data generated or analyzed during this study are included in this published article.