Abstract
Gestational diabetes mellitus (GDM) is known as different degree glucose intolerance that is initially identified during pregnancy. MicroRNAs (miRs) may be a potential candidate for treatment of GDM. Herein, we suggested that miR-351 could be an inhibitor in the progression of GDM via the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway. Microarray analysis was used to identify differentially expressed genes and predict miRs regulating flotillin 2 (FLOT2). Target relationship between miR-351 and FLOT2 was verified. Gestational diabetes mellitus mice were treated with a series of mimic, inhibitor and small interfering RNA to explore the effect of miR-351 on insulin resistance (IR), cell apoptosis in pancreatic tissues and liver gluconeogenesis through evaluating GDM-related biochemical indexes, as well as expression of miR-351, FLOT2, PI3K/AKT pathway-, IR- and liver gluconeogenesis-related genes. MiR-351 and FLOT2 were reported to be involved in GDM. FLOT2 was the target gene of miR-351. Gestational diabetes mellitus mice exhibited IR and liver gluconeogenesis, up-regulated FLOT2, activated PI3K/AKT pathway and down-regulated miR-351 in liver tissues. Additionally, miR-351 overexpression and FLOT2 silencing decreased the levels of FLOT2, phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, fasting blood glucose, fasting insulin, total cholesterol, triglyceride, glyeosylated haemoglobin and homeostasis model of assessment for IR index (HOMA-IR), extent of PI3K and AKT phosphorylation, yet increased the levels of HOMA for islet β-cell function, HOMA for insulin sensitivity index and glucose transporter 2 expression, indicating reduced cell apoptosis in pancreatic tissues and alleviated IR and liver gluconeogenesis. Our results reveal that up-regulation of miR-351 protects against IR and liver gluconeogenesis by repressing the PI3K/AKT pathway through regulating FLOT2 in GDM mice, which identifies miR-351 as a potential therapeutic target for the clinical management of GDM.