microRNA-503 contribute to pancreatic ß cell dysfunction by targeting the mTOR pathway in gestational diabetes mellitus
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Date
2017-10-27
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Abstract
Loss of pancreatic β cells is involved in pathogenesis of gestational diabetes mellitus (GDM).
Recently, several studies have elucidated the connection between microRNAs (miRNAs) and diabetes
mellitus (DM), but the role of miRNAs in GDM remains unclear. The aim of this study was to evaluate
the potential functions of miRNAs in GDM and to investigate the underlying mechanisms of action.
First, we explored the expression profile of miRNAs in placenta tissue from GDM patients using
microarray. Validation analysis was performed in peripheral blood specimens using quantitative
reverse transcription PCR (qRT-PCR). Then the role and regulating mechanism of miR-503 in weaken
the function of pancreatic β cell was investigated. We found that miR-503 was markedly upregulated
in placenta tissue from GDM patients, as elevated in peripheral blood specimens, and the high level
was positively correlated to blood glucose concentration. Knockdown of miR-503 enhanced insulin
secretion of pancreatic β-cells, promoted cell proliferation and protected cells from apoptosis,
whereas overexpression of miR- 503 showed the opposite effects. Furthermore, mammalian target of
rapamycin (mTOR) was identified as a direct target of miR-503 and mTOR silencing could reverse the
improving effects of miR-503 knockdown on insulin secretion and pancreatic β-cells proliferation.
High expression of miR-503 in peripheral blood may be acted as a
unctions of pancreatic β-cells by targeting the mTOR pathway,
suggesting that targeting miR-503/mTOR axis could serve as a novel therapeutic target for GDM.
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Keywords
Gestational diabetes mellitus, microRNA-503, Pancreatic β-cells, mTOR