4.7 Article

Circulating Exosomal miR-20b-5p Is Elevated in Type 2 Diabetes and Could Impair Insulin Action in Human Skeletal Muscle

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DIABETES
卷 68, 期 3, 页码 515-526

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AMER DIABETES ASSOC
DOI: 10.2337/db18-0470

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资金

  1. Strategic Diabetes Program at Karolinska Institute
  2. European Research Council Ideas Program (ICEBERG) [ERC-2008-AdG23285]
  3. Vetenskapsradet (Swedish Research Council) [2011-3550, 2012-1760, 2015-165]
  4. Swedish Diabetes Foundation [DIA2015-032, DIA2015-052]
  5. Stiftelsen for Strategisk Forskning (Swedish Foundation for Strategic Research) [SRL10-0027]
  6. Diabetes Wellness Sweden
  7. Novo Nordisk Foundation [NNF14OC0009941]
  8. Swedish Research Council for Sport Science [FO2016-0005]
  9. Swedish Heart Lung Foundation [20150423]
  10. Stockholm Lans Landsting (Stockholm County Council)
  11. Swedish Foundation for Strategic Research (SSF) [SRL10-0027] Funding Source: Swedish Foundation for Strategic Research (SSF)

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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.

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