Downregulation of microRNA-873 attenuates insulin resistance and myocardial injury in rats with gestational diabetes mellitus by upregulating IGFBP2

Abstract

Gestational diabetes mellitus (GDM) is a metabolic disorder characterized by insulin resistance, and patients with GDM have a higher risk of cardiovascular disease. Multiple microRNAs (miRNAs) are reported to be involved in the regulation of myocardial injury. Moreover, miR-873 was predicted to target insulin-like growth factor binding protein 2 (IGFBP2) through bioinformatic analysis, which was further confirmed using a luciferase assay. Thus, our objective was to assess whether microRNA-873 (miR-873) affects insulin resistance and myocardial injury in an established GDM rat model. The GDM rats were treated with miR-875 mimic or inhibitor or IGFBP2 siRNA. The effects of miR-875 and IGFBP2 on the cardiac function, insulin resistance, and myocardial injury were evaluated by hemodynamic measurements, determination of biochemical indices of myocardium and serum, and insulin homeostatic model assessment. The results indicated that downregulation of miR-873 upregulated the expression of IGFBP2 and promoted the activation of phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) axis. With downregulation of miR-873 in GDM rats, the cardiac function was improved and the myocardial apoptosis was inhibited, coupled with elevated activity of superoxide dismutase, carbon monoxide synthase, and the nitric oxide content. In addition, the inhibition of miR-873 in GDM rats modulated the insulin resistance and reduced myocardial apoptosis. Overall, the data showed that inhibition of miR-873 by targeting IGFBP2 may regulate the insulin resistance and curtail myocardial injury in GDM rats through activating the PI3K/AKT/mTOR axis, thus providing a potential means of impeding the progression of GDM.