期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 290, 期 33, 页码 20284-20294出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M115.658625
关键词
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资金
- Helmholtz Gemeinschaft
- ERC [IsletVasc 260744]
- Fritz Thyssen Stiftung
- Deutsches Zentrum fuer Herz-Kreislauf Forschung, E.V. (DZHK)
- Israeli Science Foundation (ISF) [840/2014]
- Swedish Research Council
- Swedish Diabetes Association
In response to fasting or hyperglycemia, the pancreatic beta-cell alters its output of secreted insulin; however, the pathways governing this adaptive response are not entirely established. Although the precise role of microRNAs (miRNAs) is also unclear, a recurring theme emphasizes their function in cellular stress responses. We recently showed that miR-184, an abundant miRNA in the beta-cell, regulates compensatory proliferation and secretion during insulin resistance. Consistent with previous studies showing miR-184 suppresses insulin release, expression of this miRNA was increased in islets after fasting, demonstrating an active role in the beta-cell as glucose levels lower and the insulin demand ceases. Additionally, miR-184 was negatively regulated upon the administration of a sucrose-rich diet in Drosophila, demonstrating strong conservation of this pathway through evolution. Furthermore, miR-184 and its target Argonaute2 remained inversely correlated as concentrations of extracellular glucose increased, underlining a functional relationship between this miRNA and its targets. Lastly, restoration of Argonaute2 in the presence of miR-184 rescued suppression of miR-375-targeted genes, suggesting these genes act in a coordinated manner during changes in the metabolic context. Together, these results highlight the adaptive role of miR-184 according to glucose metabolism and suggest the regulatory role of this miRNA in energy homeostasis is highly conserved.
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