MiR-184 expression is regulated by AMPK in pancreatic islets
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
AMPK is a critical energy sensor and target for widely used antidiabetic drugs. In β cells, elevated glucose concentrations lower AMPK activity, and the ablation of both catalytic subunits [β-cell-specific AMPK double-knockout (βAMPKdKO) mice] impairs insulin secretion in vivo and β-cell identity. MicroRNAs (miRNAs) are small RNAs that silence gene expression that are essential for pancreatic β-cell function and identity and altered in diabetes. Here, we have explored the miRNAs acting downstream of AMPK in mouse and human β cells. We identified 14 down-regulated and 9 up-regulated mi RNAs in β AMPKdKO vs. control islets. Gene ontology analysis of targeted transcripts revealed enrichmentinpathways important for β-cell function and identity. The most down-regulated miRNA wasmiR-184 (miR-184-3p), an important regulator of β-cell function and compensatory expansion that is controlled by glucose and reduced in diabetes. We demonstrate that AMPK is a potent regulator and an important mediator of the negative effects of glucose on miR-184 expression. Additionally, we reveal sexual dimorphism in miR-184 expression in mouse and human islets. Collectively, these data demonstrate that glucose-mediated changes in AMPK activity arecentral for there gulation of miR-184 and other miRNAs in is lets and provide a link between energy status and gene expression in β cells.
Originalsprog | Engelsk |
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Tidsskrift | FASEB Journal |
Vol/bind | 32 |
Udgave nummer | 5 |
Sider (fra-til) | 2587-2600 |
Antal sider | 14 |
ISSN | 0892-6638 |
DOI | |
Status | Udgivet - maj 2018 |
Eksternt udgivet | Ja |
ID: 238433779