MiR‐184 expression is regulated by AMPK in pancreatic islets
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| Názov: | MiR‐184 expression is regulated by AMPK in pancreatic islets |
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| Autori: | Martinez-Sanchez, Aida, Nguyen-Tu, Marie-Sophie, Cebola, Ines, Yavari, Arash, Marchetti, Piero, Piemonti, Lorenzo, De Koning, Eelco, Shapiro, A. M. James, Johnson, Paul, Sakamoto, Kei, Smith, David M., Leclerc, Isabelle, Ashrafian, Houman, Ferrer, Jorge, Rutter, Guy A. |
| Prispievatelia: | Hubrecht Institute with UMC, Regenerative Medicine and Stem Cells, Medical Research Council (MRC), Wellcome Trust, Pathology/molecular and cellular medicine |
| Zdroj: | FASEB J |
| Informácie o vydavateľovi: | Wiley, 2017. |
| Rok vydania: | 2017 |
| Predmety: | Life Sciences & Biomedicine - Other Topics, Male, 0301 basic medicine, diabetes, glucose, miRNAs, β-cell, MICRORNAS, Diabetes Mellitus/genetics, β cell, Mirnas, AMP-Activated Protein Kinases, Biochemistry, Mice, Insulin-Secreting Cells, AMP-Activated Protein Kinases/genetics, Mice, Knockout, 2. Zero hunger, B cell, Sex Characteristics, Diabetes, GLUCOSE-METABOLISM, CANCER, MIRNAS, Glucose, Biotechnology, Molecular Biology, Genetics, Female, Life Sciences & Biomedicine, Glucose/genetics, Biochemistry & Molecular Biology, mice, MODELS, MicroRNAs/biosynthesis, Cell Line, 03 medical and health sciences, Insulin-Secreting Cells/metabolism, STIMULATED INSULIN-SECRETION, BETA-CELL FUNCTION, Journal Article, Diabetes Mellitus, Animals, Humans, Biology, Energy Metabolism/genetics, Science & Technology, Research, 0601 Biochemistry And Cell Biology, Cell Biology, PROTEIN-KINASE, 0606 Physiology, beta cell, MICE, MicroRNAs, Gene Expression Regulation, 1116 Medical Physiology, IDENTITY, Energy Metabolism |
| Popis: | 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 [β-cell-specific AMPK double-knockout (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. |
| Druh dokumentu: | Article Conference object Other literature type |
| Popis súboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.201701100r |
| Prístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/29269398 https://hdl.handle.net/20.500.11755/95a8ebbb-c297-41e8-a65c-fb0d709094b1 https://pure.knaw.nl/portal/en/publications/95a8ebbb-c297-41e8-a65c-fb0d709094b1 https://doi.org/10.1096/fj.201701100R https://pure.knaw.nl/portal/en/publications/mir-184-expression-is-regulated-by-ampk-in-pancreatic-islets https://www.cardioscience.ox.ac.uk/publications/812758 https://dspace.library.uu.nl/handle/1874/365465 https://onlinelibrary.wiley.com/doi/abs/10.1096/fj.201701100R https://arpi.unipi.it/handle/11568/925182 https://www.rdm.ox.ac.uk/publications/812758 https://dspace.library.uu.nl/handle/1874/365465 https://hdl.handle.net/1887/86707 http://hdl.handle.net/10044/1/63379 https://ora.ox.ac.uk/objects/uuid:174f1b09-82fd-4d76-8e21-e64a6b4a47fc https://doi.org/10.1096/fj.201701100r https://www.fasebj.org/doi/pdf/10.1096/fj.201701100R https://hdl.handle.net/11568/925182 https://doi.org/10.1096/fj.201701100R https://biblio.vub.ac.be/vubir/mir184-expression-is-regulated-by-ampk-in-pancreatic-islets(3591a124-d938-4536-b203-a8ab0aded04d).html |
| Rights: | CC BY |
| Prístupové číslo: | edsair.doi.dedup.....fe1ca2ae72d446ef1e45b13cc99a99c3 |
| Databáza: | OpenAIRE |
| Abstrakt: | 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 [β-cell-specific AMPK double-knockout (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. |
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| ISSN: | 15306860 08926638 |
| DOI: | 10.1096/fj.201701100r |
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