MiR-184 expression is regulated by AMPK in pancreatic islets
AMPK is a critical energy sensor and target for widely used antidiabetic drugs. In β-cells, elevated glucose concentrations lower AMPK activity, and the ablation of both catalytic subunits (βAMPKdKO mice) impairs insulin secretion in vivo and β-cell identity. MicroRNAs (miRNAs) are small RNAs that s...
| Asıl Yazarlar: | , , , , , , , , , , , , , , |
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| Materyal Türü: | Journal article |
| Dil: | English |
| Baskı/Yayın Bilgisi: |
Federation of American Society of Experimental Biology
2017
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| _version_ | 1826260879666053120 |
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| author | Martinez-Sanchez, A Nguyen-Tu, M Cebola, I Yavari, A Marchetti, P Piemonti, L de Koning, E Shapiro, A Johnson, P Sakamoto, K Smith, D Leclerc, I Ashrafian, H Ferrer, J Rutter, G |
| author_facet | Martinez-Sanchez, A Nguyen-Tu, M Cebola, I Yavari, A Marchetti, P Piemonti, L de Koning, E Shapiro, A Johnson, P Sakamoto, K Smith, D Leclerc, I Ashrafian, H Ferrer, J Rutter, G |
| author_sort | Martinez-Sanchez, A |
| collection | OXFORD |
| description | AMPK is a critical energy sensor and target for widely used antidiabetic drugs. In β-cells, elevated glucose concentrations lower AMPK activity, and the ablation of both catalytic subunits (βAMPKdKO mice) impairs insulin secretion in vivo and β-cell identity. MicroRNAs (miRNAs) are small RNAs that silence gene expression that are essential for pancreatic β-cell function and identity and altered in diabetes. Here, we have explored the miRNAs acting downstream of AMPK in mouse and human β-cells. We identified 14 down-regulated and 9 up-regulated miRNAs in βAMPKdKO vs. control islets. Gene ontology analysis of targeted transcripts revealed enrichment in pathways important for β-cell function and identity. The most down-regulated miRNA was miR-184 (miR-184-3p), an important regulator of β-cell function and compensatory expansion that is controlled by glucose and reduced in diabetes. We demonstrate that AMPK is a potent regulator and an important mediator of the negative effects of glucose on miR-184 expression. Additionally, we reveal sexual dimorphism in miR-184 expression in mouse and human islets. Collectively, these data demonstrate that glucose-mediated changes in AMPK activity are central for the regulation of miR-184 and other miRNAs in islets and provide a link between energy status and gene expression in β-cells.-Martinez-Sanchez, A., Nguyen-Tu, M.-S., Cebola, I., Yavari, A., Marchetti, P., Piemonti, L., de Koning, E., Shapiro, A. M. J., Johnson, P., Sakamoto, K., Smith, D. M., Leclerc, I., Ashrafian, H., Ferrer, J., Rutter, G. A. MiR-184 expression is regulated by AMPK in pancreatic islets. |
| first_indexed | 2024-03-06T19:12:44Z |
| format | Journal article |
| id | oxford-uuid:174f1b09-82fd-4d76-8e21-e64a6b4a47fc |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:12:44Z |
| publishDate | 2017 |
| publisher | Federation of American Society of Experimental Biology |
| record_format | dspace |
| spelling | oxford-uuid:174f1b09-82fd-4d76-8e21-e64a6b4a47fc2022-03-26T10:36:31ZMiR-184 expression is regulated by AMPK in pancreatic isletsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:174f1b09-82fd-4d76-8e21-e64a6b4a47fcEnglishSymplectic Elements at OxfordFederation of American Society of Experimental Biology2017Martinez-Sanchez, ANguyen-Tu, MCebola, IYavari, AMarchetti, PPiemonti, Lde Koning, EShapiro, AJohnson, PSakamoto, KSmith, DLeclerc, IAshrafian, HFerrer, JRutter, GAMPK is a critical energy sensor and target for widely used antidiabetic drugs. In β-cells, elevated glucose concentrations lower AMPK activity, and the ablation of both catalytic subunits (βAMPKdKO mice) impairs insulin secretion in vivo and β-cell identity. MicroRNAs (miRNAs) are small RNAs that silence gene expression that are essential for pancreatic β-cell function and identity and altered in diabetes. Here, we have explored the miRNAs acting downstream of AMPK in mouse and human β-cells. We identified 14 down-regulated and 9 up-regulated miRNAs in βAMPKdKO vs. control islets. Gene ontology analysis of targeted transcripts revealed enrichment in pathways important for β-cell function and identity. The most down-regulated miRNA was miR-184 (miR-184-3p), an important regulator of β-cell function and compensatory expansion that is controlled by glucose and reduced in diabetes. We demonstrate that AMPK is a potent regulator and an important mediator of the negative effects of glucose on miR-184 expression. Additionally, we reveal sexual dimorphism in miR-184 expression in mouse and human islets. Collectively, these data demonstrate that glucose-mediated changes in AMPK activity are central for the regulation of miR-184 and other miRNAs in islets and provide a link between energy status and gene expression in β-cells.-Martinez-Sanchez, A., Nguyen-Tu, M.-S., Cebola, I., Yavari, A., Marchetti, P., Piemonti, L., de Koning, E., Shapiro, A. M. J., Johnson, P., Sakamoto, K., Smith, D. M., Leclerc, I., Ashrafian, H., Ferrer, J., Rutter, G. A. MiR-184 expression is regulated by AMPK in pancreatic islets. |
| spellingShingle | Martinez-Sanchez, A Nguyen-Tu, M Cebola, I Yavari, A Marchetti, P Piemonti, L de Koning, E Shapiro, A Johnson, P Sakamoto, K Smith, D Leclerc, I Ashrafian, H Ferrer, J Rutter, G MiR-184 expression is regulated by AMPK in pancreatic islets |
| title | MiR-184 expression is regulated by AMPK in pancreatic islets |
| title_full | MiR-184 expression is regulated by AMPK in pancreatic islets |
| title_fullStr | MiR-184 expression is regulated by AMPK in pancreatic islets |
| title_full_unstemmed | MiR-184 expression is regulated by AMPK in pancreatic islets |
| title_short | MiR-184 expression is regulated by AMPK in pancreatic islets |
| title_sort | mir 184 expression is regulated by ampk in pancreatic islets |
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