Tattikota, S.G., Rathjen, T., Hausser, J., Khedkar, A., Kabra, U.D., Pandey, V., Sury, M., Wessels, H.H., Mollet, I.G., Eliasson, L., Selbach, M., Zinzen, R.P., Zavolan, M., Kadener, S., Tschöp, M.H., Jastroch, M., Friedländer, M.R., Poy, M.N. (2015). miR-184 Regulates Pancreatic β-Cell Function According to Glucose Metabolism.  J. Biol. Chem. 290(33): 20284--20294.

FBrf0229280

Research paper

In response to fasting or hyperglycemia, the pancreatic β-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 β-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 β-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.

PMC4536436 (PMC) (EuropePMC)