TY - JOUR
T1 - miR-184 regulates pancreatic β-cell function according to glucose metabolism
AU - Tattikota, Sudhir G.
AU - Rathjen, Thomas
AU - Hausser, Jean
AU - Khedkar, Aditya
AU - Kabra, Uma D.
AU - Pandey, Varun
AU - Sury, Matthias
AU - Wessels, Hans Hermann
AU - Mollet, Inês G.
AU - Eliasson, Lena
AU - Selbach, Matthias
AU - Zinzen, Robert P.
AU - Zavolan, Mihaela
AU - Kadener, Sebastian
AU - Tschöp, Matthias H.
AU - Jastroch, Martin
AU - Friedländer, Marc R.
AU - Poy, Matthew N.
N1 - Publisher Copyright:
© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2015/8/14
Y1 - 2015/8/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84939825167&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84939825167&partnerID=8YFLogxK
U2 - 10.1074/jbc.M115.658625
DO - 10.1074/jbc.M115.658625
M3 - Article
C2 - 26152724
AN - SCOPUS:84939825167
SN - 0021-9258
VL - 290
SP - 20284
EP - 20294
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 33
ER -