Abstract
miRNAs are noncoding RNAs representing an important class of gene expression modulators. Extracellular circulating miRNAs are both candidate biomarkers for disease pathogenesis and mediators of cell-to-cell communication. We examined the miRNA expression profile of total serum and serum-derived exosome-enriched extracellular vesicles in people with normal glucose tolerance or type 2 diabetes. In contrast to total serum miRNA, which did not reveal any differences in miRNA expression, we identified differentially abundant miRNAs in patients with type 2 diabetes using miRNA expression profiles of exosome RNA (exoRNA). To validate the role of these differentially abundant miRNAs on glucose metabolism, we transfected miR-20b-5p, a highly abundant exoRNA in patients with type 2 diabetes, into primary human skeletal muscle cells. miR-20b-5p overexpression increased basal glycogen synthesis in human skeletal muscle cells. We identified AKTIP and STAT3 as miR-20b-5p targets. miR-20b-5p overexpression reduced AKTIP abundance and insulin-stimulated glycogen accumulation. In conclusion, exosome-derived extracellular miR-20b-5p is a circulating biomarker associated with type 2 diabetes that plays an intracellular role in modulating insulin-stimulated glucose metabolism via AKT signaling.