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A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals
Published on: June 25, 2018
miR-210-3p Impairs Pancreatic β-Cell Function by Targeting Dtx1 in Gestational Diabetes Mellitus
Xiaohui Cao1, Bin Lu2, Ying Gu3
1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Canglang District, Suzhou, 215006 Jiangsu, China; Department of Obstetrics, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi, Jiangsu 214002, China.
Abstract:
Gestational diabetes mellitus (GDM), a common complication in pregnancy, could threaten the health of both pregnancies and their offspring. miR-210-3p has been reported that play a crucial role in many diseases. Nevertheless, the molecular mechanism and clinical significance of miR-210-3p in the GDM is still unclear. miR-210-3p was overexpressed in the pancreas of the GDM mouse model. Meanwhile, miR-210-3p weakens cell viability and promotes the apoptosis of pancreatic β cells, impairing the function of pancreatic β cells. Bioinformatics analysis showed that miR-210-3p directly targets the expression of Dtx1, and miR-210-3p negatively regulated dtx1. Down-expression of Dtx1 could increase the expression of insulin and boost the function of pancreatic β cells through inhibiting expressions of p-Akt, p-mTOR, p-4E-BP1, and p-SGK1. Rescue experiments verified that miR-210-3p could regulate the function of pancreatic β cells and adjust the content of TG, TC, and HDL in the blood of mice with GDM via regulating the expression of Dtx1. The study demonstrated that miR-210-3p is significantly overexpressed in the pancreas of the GDM mouse model, which could impair the function and cell viability of pancreatic β cells via suppressing the expression of Dtx1 promotes the progression of GDM. These findings provide a novel strategy to treat GDM.
Insights
MicroRNA-210-3p (miR-210-3p) is overexpressed in gestational diabetes mellitus (GDM), impairing pancreatic beta cell function by targeting Dtx1. This research offers a new therapeutic strategy for GDM.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Gestational diabetes mellitus (GDM) poses significant risks to maternal and infant health.
- MicroRNA-210-3p (miR-210-3p) is implicated in various diseases, but its role in GDM remains unclear.
Purpose of the Study:
- To elucidate the molecular mechanism and clinical significance of miR-210-3p in GDM.
- To investigate the regulatory role of miR-210-3p on pancreatic beta cell function in GDM.
Main Methods:
- Utilized a GDM mouse model to assess miR-210-3p expression in pancreatic tissue.
- Employed bioinformatics analysis to identify miR-210-3p targets, followed by in vitro and in vivo rescue experiments.
- Assessed pancreatic beta cell viability, apoptosis, insulin expression, and blood lipid profiles (TG, TC, HDL).
Main Results:
- miR-210-3p was significantly overexpressed in the pancreas of GDM mice.
- miR-210-3p impaired pancreatic beta cell viability and function by targeting and downregulating Dtx1.
- Downregulation of Dtx1 affected insulin expression and key signaling pathways (Akt, mTOR, 4E-BP1, SGK1).
- miR-210-3p regulated GDM-associated blood lipid levels via Dtx1 modulation.
Conclusions:
- miR-210-3p promotes GDM progression by suppressing Dtx1, leading to impaired pancreatic beta cell function.
- Targeting miR-210-3p presents a potential novel therapeutic strategy for managing GDM.
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