Data Entry: Please note that the research database will be replaced by UNIverse by the end of October 2023. Please enter your data into the system https://universe-intern.unibas.ch. Thanks
Argonaute2 Mediates Compensatory Expansion of the Pancreatic β Cell
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID
2326282
Author(s)
Tattikota, Sudhir G; Rathjen, Thomas; McAnulty, Sarah J; Wessels, Hans-Hermann; Akerman, Ildem; van de Bunt, Martijn; Hausser, Jean; Esguerra, Jonathan L S; Musahl, Anne; Pandey, Amit K; You, Xintian; Chen, Wei; Herrera, Pedro L; Johnson, Paul R; O'Carroll, Donal; Eliasson, Lena; Zavolan, Mihaela; Gloyn, Anna L; Ferrer, Jorge; Shalom-Feuerstein, Ruby; Aberdam, Daniel; Poy, Matthew N
Argonaute2 Mediates Compensatory Expansion of the Pancreatic β Cell
Journal
Cell metabolism
Volume
19
Number
1
Pages / Article-Number
122-34
Abstract
Pancreatic β cells adapt to compensate for increased metabolic demand during insulin resistance. Although the microRNA pathway has an essential role in β cell proliferation, the extent of its contribution is unclear. Here, we report that miR-184 is silenced in the pancreatic islets of insulin-resistant mouse models and type 2 diabetic human subjects. Reduction of miR-184 promotes the expression of its target Argonaute2 (Ago2), a component of the microRNA-induced silencing complex. Moreover, restoration of miR-184 in leptin-deficient ob/ob mice decreased Ago2 and prevented compensatory β cell expansion. Loss of Ago2 during insulin resistance blocked β cell growth and relieved the regulation of miR-375-targeted genes, including the growth suppressor Cadm1. Lastly, administration of a ketogenic diet to ob/ob mice rescued insulin sensitivity and miR-184 expression and restored Ago2 and β cell mass. This study identifies the targeting of Ago2 by miR-184 as an essential component of the compensatory response to regulate proliferation according to insulin sensitivity.