Poster Presentation Australasian Diabetes in Pregnancy Society and Society of Obstetric Medicine Australia and New Zealand Joint Scientific Meeting 2021

Gestational diabetes mellitus is associated with changes in the microRNA expression in extracellular vesicles and potential role of miR-92a-3p in skeletal muscle insulin sensitivity (#133)

Soumyalekshmi Nair 1 , Dominic Guanzon 1 , Katherin Scholz-Romero 1 , Carlos Palma 1 , Martha Lappas 2 3 , Harold David McIntyre 4 , Gregory Rice 1 , Carlos Salomon 1 5
  1. University of Queensland-Centre for Clinical Research, Brisbane, QLD, Australia
  2. Department of Obstetrics and Gynaecology, , University of Melbourne, Melbourne, Victoria, Australia
  3. Mercy Perinatal Research Centre, Mercy Hospital for Women, Melbourne, Victoria, Australia
  4. Mater Research, Faculty of Medicine, The University of Queensland, Mater Health, South Brisbane, Australia
  5. Department of Clinical Biochemistry and Immunology, , Faculty of Pharmacy, University of Concepción, , Concepción, Chile

Extracellular vesicles (EVs) play important roles in cell communication in physiological and pathological contexts. The aim of this study was to identify the role of circulating small EVs (sEVs) in the regulation of maternal insulin sensitivity in Gestational Diabetes Mellitus (GDM). sEVs were isolated from maternal plasma obtained at early, mid and late gestation (GDM=8, Normal Glucose Tolerant (NGT)=14) and a panel of miRNAs were quantified by real-time PCR. The potential targets of the miRNAs were identified and effect on skeletal muscle insulin sensitivity was analyzed by glucose uptake assay. We identified that six miRNAs namely miR-16-2-3p, miR-16-5p, miR-1910-5p, miR-423-5p, miR-92a-3p, and miR-92b-3p were differentially expressed in GDM compared to NGT pregnancies. On bioinformatic analysis these miRNAs were targeting the pathways associated with glucose homeostasis particularly the insulin response and JAK/STAT pathway. We analyzed the specific pattern of expression of these miRNAs across gestation. Interestingly, miR-92a-3p expression was higher in GDM than NGT in the second trimester, whereas it in the third trimester the expression is lower in GDM than NGT. Using a PCR array, we identified that miR-92a-3p induces the expression of SOCS (Suppressor of Cytokine Signaling)-2 and suppress the expression of NOS (Nitric Oxide Synthase)-2 in the JAK/STAT signaling pathway in skeletal muscle cells. Also, in the glucose uptake assay, miR-92a-3p increased the insulin-stimulated glucose uptake compared to negative miRNA in primary skeletal muscle cells. Together, the pattern of expression of miR-92a-3p in circulating sEVs in GDM and its impact on skeletal muscle insulin response indicate a protective mechanism of this miRNA to reduce the hyperglycemia in GDM. This study shows that sEV-associated miRNAs may contribute the pathophysiology of insulin resistance and maternal metabolic changes in GDM. Finally, we identify that miR-92a-3p in circulating EVs in GDM can target JAK/STAT signaling and regulate insulin sensitivity in skeletal muscle cells.