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.