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

Journal article
Authors Mutsumi Katayama
Oscar P B Wiklander
Tomas Fritz
Kenneth Caidahl
Samir El- Andaloussi
Juleen R Zierath
Anna Krook
Published in Diabetes
Volume 68
Issue 3
Pages 515-526
ISSN 1939-327X
Publication year 2018
Published at Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 515-526
Language en
Links dx.doi.org/10.2337/db18-0470
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Cell biology, Endocrinology and Diabetes, Clinical Laboratory Medicine

Abstract

MicroRNAs (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 type 2 diabetes patients 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 type 2 diabetic patients, 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, which plays an intracellular role in modulating insulin-stimulated glucose metabolism via AKT signaling.

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