Exosomal Circular RNA hsa_circ_0046060 of Umbilical Cord Mesenchymal Stromal Cell Ameliorates Glucose Metabolism and Insulin Resistance in Gestational Diabetes Mellitus via the miR-338-3p/G6PC2 Axis

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Impaired glucose metabolism and insulin sensitivity have been linked to the pathogenesis of gestational diabetes mellitus (GDM). Exosomes secreted by the umbilical cord mesenchymal stromal cells (UMSCs) and circular RNAs (circRNAs) derived from exosomes have been shown to be associated with the progression of GDM-related complications. Methods UMSCs were isolated from umbilical cords and identified through flow cytometry. Exosomes were isolated from UMSCs and were then characterized. The expression levels of RNA of hsa_circ_0046060, mmu_circ_0002819, and miR-338-3p were determined by quantitative real-time polymerase chain reaction (RT-qPCR). The intracellular glucose intake and glycogen content were measured using a High Sensitivity Glucose Assay Kit and Glycogen Assay Kit, respectively. Bioinformatics analysis and luciferase reporter assay were used to validate interactions among hsa_circ_0046060, miR-338-3p, and G6PC2. The expression of insulin receptor substrate-1 (IRS-1) and its phosphorylated form, (p-IRS-1), as well as G6PC2, was determined through western blotting. Results UMSCs and exosomes were successfully isolated and identified. The upregulation of hsa_circ_0046060 decreased the intracellular glucose content in L-02 cells (43.45 vs. 16.87 pM/mg, P =0.0002), whereas shRNA-mediated downregulation reversed this effect (16.87 vs. 33.16 pM/mg, P =0.0011). Mmu

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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