Argonaute2 mediates compensatory expansion of the pancreatic β cell.
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-resist...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Cell Press
2014
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| _version_ | 1797077935790751744 |
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| author | Tattikota, S Rathjen, T McAnulty, S Wessels, H Akerman, I van de Bunt, M Hausser, J Esguerra, J Musahl, A Pandey, A You, X Chen, W Herrera, P Johnson, P O'Carroll, D Eliasson, L Zavolan, M Gloyn, A Ferrer, J Shalom-Feuerstein, R Aberdam, D Poy, M |
| author_facet | Tattikota, S Rathjen, T McAnulty, S Wessels, H Akerman, I van de Bunt, M Hausser, J Esguerra, J Musahl, A Pandey, A You, X Chen, W Herrera, P Johnson, P O'Carroll, D Eliasson, L Zavolan, M Gloyn, A Ferrer, J Shalom-Feuerstein, R Aberdam, D Poy, M |
| author_sort | Tattikota, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T00:25:11Z |
| format | Journal article |
| id | oxford-uuid:7de856e0-48a7-4d30-9bcf-2b22e061cbb3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:25:11Z |
| publishDate | 2014 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:7de856e0-48a7-4d30-9bcf-2b22e061cbb32022-03-26T21:06:45ZArgonaute2 mediates compensatory expansion of the pancreatic β cell.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7de856e0-48a7-4d30-9bcf-2b22e061cbb3EnglishSymplectic Elements at OxfordCell Press2014Tattikota, SRathjen, TMcAnulty, SWessels, HAkerman, Ivan de Bunt, MHausser, JEsguerra, JMusahl, APandey, AYou, XChen, WHerrera, PJohnson, PO'Carroll, DEliasson, LZavolan, MGloyn, AFerrer, JShalom-Feuerstein, RAberdam, DPoy, MPancreatic 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. |
| spellingShingle | Tattikota, S Rathjen, T McAnulty, S Wessels, H Akerman, I van de Bunt, M Hausser, J Esguerra, J Musahl, A Pandey, A You, X Chen, W Herrera, P Johnson, P O'Carroll, D Eliasson, L Zavolan, M Gloyn, A Ferrer, J Shalom-Feuerstein, R Aberdam, D Poy, M Argonaute2 mediates compensatory expansion of the pancreatic β cell. |
| title | Argonaute2 mediates compensatory expansion of the pancreatic β cell. |
| title_full | Argonaute2 mediates compensatory expansion of the pancreatic β cell. |
| title_fullStr | Argonaute2 mediates compensatory expansion of the pancreatic β cell. |
| title_full_unstemmed | Argonaute2 mediates compensatory expansion of the pancreatic β cell. |
| title_short | Argonaute2 mediates compensatory expansion of the pancreatic β cell. |
| title_sort | argonaute2 mediates compensatory expansion of the pancreatic β cell |
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