Jinghong RAO, Youfang CHEN, Jingying HUANG, Ruoying WU, Yuling GAO, Xuan CHEN, Zhenzhu DONG

Inhibiting miR-182-3p Alleviates Gestational Diabetes Mellitus by Improving Insulin Resistance in Skeletal Muscle

Background: Gestational diabetes mellitus (GDM) is one of the most common metabolic diseases occurring during pregnancy. MiR-182- 3p participates in a variety of physiological processes such as cell proliferation, apoptosis, differentiation, and migration5, but its role in GDM is largely unknown. Aims: To investigate the relationship between miRNA-182-3p and GDM and explore a potential therapeutic strategy for GDM. Study Design: Animal experimentation Methods: To evaluate the effect of miRNA182-3p in GDM, mice were separated as negative control (NC), miRNA-182-3p mimic or miRNA-182-3p inhibitor, and miRNAs were administered intraperitoneally. Additionally, miRNA-182-3p mimic or miRNA-182-3p inhibitor was transfected into C2C12 cells to evaluate glucose metabolism and insulin-related pathways. Results: The miR-182-3p mimic accelerated GDM, which was effectively reversed by the inhibitor in GDM mice (P = 0.005, miR- 182-3p inhibitor vs. mimic). Insulin receptor 1 (INSR1) was predicted to be the direct target gene of miR-182-3p using online tools. In addition, the miR-182-3p mimic inhibited INSR1 expression and insulin-related pathways in vivo and in vitro, which were all reversed by the miRNA82-3p inhibitor. Furthermore, the miR-182-3p mimic impaired glucose uptake and consumption by inhibiting translocation of glucose transporter type 4 (GLUT4) toward the C2C12 cell membrane (P = 0.007 vs. control), while the inhibitor accelerated these processes (P = 0.032 vs. control; P = 0.005, miRNA-182-3p inhibitor vs. mimic). Conclusion: Inhibiting miR-182-3p effectively alleviated the development of GDM through INSR1, suggesting a potential therapeutic strategy for GDM.

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