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

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.

• Authors: Mutsumi Katayama, Oscar P B Wiklander, Tomas Fritz, Kenneth Caidahl, Samir El-Andaloussi, Juleen R Zierath, Anna Krook
• Journal: Diabetes (Diabetes) Vol. 68 Issue 3 Pg. 515-526 (03 2019) ISSN: 1939-327X [Electronic] United States
• PMID: 30552111 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 by the American Diabetes Association.

Chemical References

• AKTIP protein, human
• Adaptor Proteins, Signal Transducing
• Apoptosis Regulatory Proteins
• Insulin
• MIRN20a microRNA, human
• MicroRNAs
• STAT3 Transcription Factor

Topics

• Adaptor Proteins, Signal Transducing (genetics, metabolism)
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Diabetes Mellitus, Type 2 (blood, metabolism, pathology)
• Exosomes (metabolism)
• Humans
• Insulin (blood, metabolism)
• MicroRNAs (blood, genetics, metabolism)
• Middle Aged
• Muscle, Skeletal (metabolism)
• STAT3 Transcription Factor (blood, metabolism)
• Signal Transduction