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| Status |
Public on Jan 10, 2019 |
| Title |
Circulating Exosomal miR-20b-5p is Elevated in Type 2 Diabetes and Could Impair Insulin Action in Human Skeletal Muscle. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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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| Overall design |
The purpose of this study was to validate the role of differentially abundant miRNAs on glucose metabolism. We transfected miR-20b, a highly abundant exoRNA in type 2 diabetic patient exosomes, into primary human skeletal muscle cells.
We used microarrays to detail the global regulation of gene expression by miR-20b and identified up- and down-regulated genes by miR-20b in primary human skeletal muscle cells.
To search for target genes of miR-20b, we performed transcriptome analysis to compare expression profiles between human skeletal muscle cells transfected with miR-20b and those transfected with a negative control.
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| Web link |
http://diabetes.diabetesjournals.org/content/early/2018/12/09/db18-0470
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| Contributor(s) |
Krook A, Katayama M |
| Citation(s) |
30552111 |
| Submission date |
Aug 06, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Mutsumi Katayama |
| E-mail(s) |
mutsumi.katayama@ki.se
|
| Phone |
852482263
|
| Organization name |
Karolinska Institutet
|
| Department |
Physiology and Pharmacology
|
| Lab |
Integrative Physiology
|
| Street address |
Solnavägen 9
|
| City |
Stockholm |
| ZIP/Postal code |
17177 |
| Country |
Sweden |
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| Platforms (1) |
| GPL16686 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| GSM2733443 |
hskm cells_negative control-transfected_subject1 |
| GSM2733444 |
hskm cells_miR20b-transfected_subject1 |
| GSM2733445 |
hskm cells_negative control-transfected_subject2 |
| GSM2733446 |
hskm cells_miR20b-transfected_subject2 |
| GSM2733447 |
hskm cells_negative control-transfected_subject3 |
| GSM2733448 |
hskm cells_miR20b-transfected_subject3 |
|
| Relations |
| BioProject |
PRJNA397344 |
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