Identification of Neuroendocrine Stress Response-Related Circulating MicroRNAs as Biomarkers for Type 2 Diabetes Mellitus and Insulin Resistance

Abstract

BackgroundChronic stress plays an important role in the development of type 2 diabetes mellitus (T2DM) and insulin resistance (IR). MicroRNAs (miRNAs) play key roles in mediating stress responses by regulating the expression of target genes. This study systematically screened and identified the neuroendocrine stress response-related circulating miRNAs which are associated with T2DM and IR.MethodsBased on the differential plasma expression profiles between individuals with and without T2DM, stress-related miRNAs were selected from those differently expressed miRNAs whose targets are involved in known neuroendocrine pathway of stress response. Candidate miRNAs were further validated by quantitative real-time polymerase chain reaction in a large sample, including 112 T2DM patients, 72 individuals with impaired fasting glucose (IFG), and 94 healthy controls. The association between miRNA expression and potential risk of T2DM and IFG was assessed by multivariate logistic regression models. The miRNA predictors of IR were identified by stepwise multiple regression analysis. The diagnostic performance for T2DM was evaluated by area under the curve (AUC) of receiver operating characteristic (ROC).Resultslet-7b, let-7i, miR-142, miR-144, miR-155, and miR-29a were selected as candidate miRNAs for validation. Increased expression of let-7b, miR-144, and miR-29a and decreased expression of miR-142 were significant independent predictors of T2DM, IFG, and IR (P < 0.0125). These miRNAs significantly correlated with stress hormone levels (P < 0.0125). A three-miRNA panel, including let-7b, miR-142, and miR-144 had a high accuracy for diagnosing T2DM (AUC = 0.871, 95% CI: 0.822–0.919).Conclusionlet-7b, miR-142, miR-144, and miR-29a in plasma may be important markers of neuroendocrine stress response and may play a role in the pathogenesis of T2DM and IR.

MiR-323b-5p acts as a novel diagnostic biomarker for critical limb ischemia in type 2 diabetic patients

“…Increasing evidence suggests that miRNAs play a significant role in the diagnosis of T2DM or as therapeutic targets 48 – 50 and may also regulate endothelial cell function and angiogenesis 51 , 52 . In this study, we found significant differences in the serum miRNA expression profiles of Han Chinese T2DM patients with or without CLI.…”

MicroRNA Signatures as Future Biomarkers for Diagnosis of Diabetes States

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Circulating exosomal miR-144-3p inhibits the mobilization of endothelial progenitor cells post myocardial infarction via regulating the MMP9 pathway

“…Besides, transmission electron microscopy showed that exosome had a diameter of ~100 nm ( Figure 1B ), which was in accordance with the reported size. Based on previous studies which profiled circulating microRNAs of type 1 and 2 diabetes [ 13 , 14 ], we focused on the most dysregulated miR-144-3p. Similarly, compared with the circulating exosome from normal mice (NGexo), qPCR (n=3 each group) confirmed miR-144-3p was upregulated in diabetic exosomes (DMexo; Figure 1C ).…”