miR-184 Regulates Pancreatic ß-Cell Function According to Glucose Metabolism.
J Biol Chem
; 290(33): 20284-94, 2015 Aug 14.
Article
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| MEDLINE
| ID: mdl-26152724
ABSTRACT
In response to fasting or hyperglycemia, the pancreatic ß-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 ß-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 ß-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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Islotes Pancreáticos
/
MicroARNs
/
Glucosa
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
2015
Tipo del documento:
Article
País de afiliación:
Alemania