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miRNAs control insulin content in pancreatic β‐cells via downregulation of transcriptional repressors
Open accessAbstract
MicroRNAs (miRNAs) were shown to be important for pancreas development, yet their roles in differentiated β-cells remain unclear. Here, we show that miRNA inactivation in β-cells of adult mice results in a striking diabetic phenotype. While islet architecture is intact and differentiation markers are maintained, Dicer1-deficient β-cells show a dramatic decrease in insulin content and insulin mRNA. As a consequence of the change in insulin content, the animals become diabetic. We provide evidence for involvement of a set of miRNAs in regulating insulin synthesis. The specific knockdown of miR-24, miR-26, miR-182 or miR-148 in cultured β-cells or in isolated primary islets downregulates insulin promoter activity and insulin mRNA levels. Further, miRNA-dependent regulation of insulin expression is associated with upregulation of transcriptional repressors, including Bhlhe22 and Sox6. Thus, miRNAs in the adult pancreas act in a new network that reinforces insulin expression by reducing the expression of insulin transcriptional repressors.
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“a variety of microRNAs have been shown to influence pancreatic beta cell development and function.”
From The Vasculature in Prediabetes (2018) · cites this paper as [137]
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Cites
MicroRNAs: Target Recognition and Regulatory Functions
Bartel, D. P. (2009) · Cell · doi:10.1016/j.cell.2009.01.002 · Cited by 20,068
The nuclear RNase III Drosha initiates microRNA processing
Lee, Y., Ahn, C., Han, J., Choi, H., Kim, J., Yim, J., Lee, J., Provost, P., Rådmark, O., Kim, S., et al. (2003) · Nature · doi:10.1038/nature01957 · Cited by 5,299
Role for a bidentate ribonuclease in the initiation step of RNA interference
Bernstein, E., Caudy, A. A., Hammond, S. M., & Hannon, G. J. (2001) · Nature · doi:10.1038/35053110 · Cited by 5,018
Combinatorial microRNA target predictions
Krek, A., Grün, D., Poy, M. N., Wolf, R., Rosenberg, L., Epstein, E. J., MacMenamin, P., da Piedade, I., Gunsalus, K. C., Stoffel, M., et al. (2005) · Nature Genetics · doi:10.1038/ng1536 · Cited by 4,603
Method for the Isolation of Intact Islets of Langerhans from the Rat Pancreas
Lacy, P. E., & Kostianovsky, M. (1967) · Diabetes · doi:10.2337/diab.16.1.35 · Cited by 2,741
The role of site accessibility in microRNA target recognition
Kertesz, M., Iovino, N., Unnerstall, U., Gaul, U., & Segal, E. (2007) · Nature Genetics · doi:10.1038/ng2135 · Cited by 2,460
Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation
Dor, Y., Brown, J., Martinez, O. I., & Melton, D. A. (2004) · Nature · doi:10.1038/nature02520 · Cited by 2,219
Self-citationA pancreatic islet-specific microRNA regulates insulin secretion
Poy, M. N., Eliasson, L., Krutzfeldt, J., Kuwajima, S., Ma, X., MacDonald, P. E., Pfeffer, S., Tuschl, T., Rajewsky, N., Rorsman, P., et al. (2004) · Nature · doi:10.1038/nature03076 · Cited by 2,102
Control of endodermal endocrine development by Hes-1
Jensen, J. N., Pedersen, E. E., Galante, P. E., Hald, J., Heller, R. S., Ishibashi, M., Kageyama, R., Guillemot, F., Serup, P., & Madsen, O. D. (2000) · Nature Genetics · doi:10.1038/71657 · Cited by 1,155
A dicer-independent miRNA biogenesis pathway that requires Ago catalysis
Cheloufi, S., Dos Santos, C. O., Chong, M. M. W., & Hannon, G. J. (2010) · Nature · doi:10.1038/nature09092 · Cited by 1,149
miR-375 maintains normal pancreatic α- and β-cell mass
Poy, M. N., Hausser, J., Trajkovski, M., Braun, M., Collins, S., Rorsman, P., Zavolan, M., & Stoffel, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810550106 · Cited by 740
The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb
Harfe, B. D., McManus, M. T., Mansfield, J. H., Hornstein, E., & Tabin, C. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504834102 · Cited by 656
Self-citationSussel, L., Kalamaras, J., Hartigan-O’Connor, D. J., Meneses, J. J., Pedersen, R. A., Rubenstein, J. L. R., & German, M. S. (1998) · Development · doi:10.1242/dev.125.12.2213 · Cited by 626
Widespread recombinase expression using FLPeR (Flipper) mice
Farley, F. W., Soriano, P. M., Steffen, L. S., & Dymecki, S. M. (2000) · genesis · doi:10.1002/1526-968x(200011/12)28:3/4 · Cited by 602
Naya, F. J., Stellrecht, C. M., & Tsai, M. (1995) · Genes & Development · doi:10.1101/gad.9.8.1009 · Cited by 595
Sander, M., Neubüser, A., Kalamaras, J., Ee, H. C., Martin, G. R., & German, M. S. (1997) · Genes & Development · doi:10.1101/gad.11.13.1662 · Cited by 592
Ouaamari, A. E., Baroukh, N., Martens, G. A., Lebrun, P., PIPELEERS, D. G., & OBBERGHEN, E. V. (2008) · Diabetes · doi:10.2337/db07-1614 · Cited by 438
MicroRNA Expression Is Required for Pancreatic Islet Cell Genesis in the Mouse
Lynn, F. C., Skewes-Cox, P., Kosaka, Y., McManus, M. T., Harfe, B. D., & German, M. S. (2007) · Diabetes · doi:10.2337/db07-0175 · Cited by 351
Plaisance, V., Abderrahmani, A., Perret-Menoud, V., Jacquemin, P., Lemaigre, F., & Regazzi, R. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601225200 · Cited by 350
MicroRNA-124a Regulates Foxa2 Expression and Intracellular Signaling in Pancreatic β-Cell Lines*
Baroukh, N., Ravier, M. A., Loder, M. K., Hill, E. V., Bounacer, A., Scharfmann, R., Rutter, G. A., & Van Obberghen, E. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611841200 · Cited by 326
Tang, X., Muniappan, L., Tang, G., & Özcan, S. (2008) · RNA · doi:10.1261/rna.1211209 · Cited by 278
Lovis, P., Gattesco, S., & Regazzi, R. (2008) · bchm · doi:10.1515/bc.2008.026 · Cited by 257
Hald, J., Hjorth, J., German, M. S., Madsen, O. D., Serup, P., & Jensen, J. N. (2003) · Developmental Biology · doi:10.1016/s0012-1606(03)00326-9 · Cited by 251
Watada, H., Kajimoto, Y., Umayahara, Y., Matsuoka, T., Kaneto, H., Fujitani, Y., Kamada, T., Kawamori, R., & Yamasaki, Y. (1996) · Diabetes · doi:10.2337/diab.45.11.1478 · Cited by 221
Gierl, M. S., Karoulias, N., Wende, H., Strehle, M., & Birchmeier, C. (2006) · Genes & Development · doi:10.1101/gad.381806 · Cited by 215
Glucose regulation of insulin gene expression in pancreatic β-cells
Andrali, S. S., Sampley, M. L., Vanderford, N. L., & Özcan, S. (2008) · Biochemical Journal · doi:10.1042/bj20081029 · Cited by 213
Petersen, H. V., Serup, P., Leonard, J. N., Michelsen, B. K., & Madsen, O. D. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.22.10465 · Cited by 207
The Islet β Cell-enriched MafA Activator Is a Key Regulator of Insulin Gene Transcription
Zhao, L., Guo, M. A., Matsuoka, T., Hagman, D. K., Parazzoli, S. D., Poitout, V., & Stein, R. W. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m409475200 · Cited by 191
microRNAs and the regulation of glucose and lipid metabolism
Poy, M. N., Spranger, M., & Stoffel, M. (2007) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2007.00775.x · Cited by 185
Qiu, Y., Guo, M. A., Huang, S., & Stein, R. W. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.2.412-420.2002 · Cited by 182
IA1 is NGN3‐dependent and essential for differentiation of the endocrine pancreas
Mellitzer, G., Bonné, S., Luco, R. F., de Casteele, M. V., Lenne‐Samuel, N., Collombat, P., Mansouri, A., Lee, J. S., Lan, M. S., PIPELEERS, D. G., et al. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601011 · Cited by 180
Kaneto, H., Miyatsuka, T., Kawamori, D., Yamamoto, K., Kato, K., Shiraiwa, T., Katakami, N., Yamasaki, Y., Matsuhisa, M., & Matsuoka, T. (2008) · Endocrine Journal · doi:10.1507/endocrj.k07e-041 · Cited by 167
Schisler, J. C., Jensen, P. B., Taylor, D. G., Becker, T. C., Knop, F. K., Takekawa, S., German, M. S., Weir, G. C., Lu, D., Mirmira, R. G., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502168102 · Cited by 158
Lan, M. S., & Breslin, M. B. (2009) · The FASEB Journal · doi:10.1096/fj.08-125971 · Cited by 142
Transcription factors regulating β-cell function
Cerf, M. E. (2006) · European Journal of Endocrinology · doi:10.1530/eje.1.02277 · Cited by 103
New pancreas from old: microregulators of pancreas regeneration
Joglekar, M. V., Parekh, V. S., & Hardikar, A. A. (2007) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2007.10.001 · Cited by 89
Iguchi, H., Ikeda, Y., Okamura, M., Tanaka, T., Urashima, Y., Ohguchi, H., Takayasu, S., Kojima, N., Iwasaki, S., Ohashi, R., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505392200 · Cited by 80
Hennessy, E., CLYNES, M. M., Jeppesen, P. B., & O’Driscoll, L. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.04.116 · Cited by 76
HES-1 Is Involved in Adaptation of Adult Human β-Cells to Proliferation In Vitro
Bar, Y., Russ, H. A., Knoller, S., Ouziel-Yahalom, L., & Efrat, S. (2008) · Diabetes · doi:10.2337/db07-1323 · Cited by 71
Moates, J. M., Nanda, S., Cissell, M. A., Tsai, M., & Stein, R. W. (2003) · Diabetes · doi:10.2337/diabetes.52.2.403 · Cited by 71
Molecular medicine of microRNAs: structure, function and implications for diabetes
Hennessy, E., & O’Driscoll, L. (2008) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399408000781 · Cited by 69
Kang, Y., Huang, X., Pasyk, E. A., Ji, J., Holz, G. G., Wheeler, M. B., Tsushima, R. G., & Gaisano, H. Y. (2002) · Diabetologia · doi:10.1007/s00125-001-0718-0 · Cited by 66
Liu, W.-D., Wang, H., Muguira, M., Breslin, M. B., & Lan, M. S. (2006) · Biochemical Journal · doi:10.1042/bj20051669 · Cited by 61
Peyton, M., Stellrecht, C. M., Naya, F. J., Huang, H., Samora, P. J., & Tsai, M. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.2.626 · Cited by 58
Transcriptional Repressors Are Increased in Pancreatic Islets of Type 2 Diabetic Rats
Inada, A., Yamada, Y., Someya, Y., Kubota, A., Yasuda, K., Ihara, Y., Kagimoto, S., Kuroe, A., Tsuda, K., & Seino, Y. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9833 · Cited by 38
Wang, H., Muguira, M., Liu, W., Zhang, T., Chen, C., Aucoin, R., Breslin, M. B., & Lan, M. S. (2008) · Journal of Endocrinology · doi:10.1677/joe-08-0001 · Cited by 25
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Xu, H., Guo, S., Li, W., & Yu, P. (2015) · Scientific Reports · doi:10.1038/srep12453 · Cited by 536
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Metadata
- Authors
- Melkman‐Zehavi, T., Oren, R., Kredo‐Russo, S., Shapira, T., Mandelbaum, A. D., Rivkin, N., Nir, T., Lennox, K. A., Behlke, M. A., Dor, Y., & Hornstein, E.
- Affiliations
- Weizmann Institute of Science (IL)
- Hebrew University of Jerusalem (IL)
- Integrated DNA Technologies (United States) (US)
- Corresponding author
- Hornstein, Eran
- Venue
- The EMBO Journal
- Published
- 2011-02-01
- Volume
- 30
- Issue
- 5
- Pages
- 835-845
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC3049206
- OpenAlex
- W2101072639
- Cited by
- 280
- References
- 46
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 10 · 2023: 9 · 2022: 17 · 2021: 21 · 2020: 23 · 2019: 18 · 2018: 16 · 2017: 23 · 2016: 16 · 2015: 34 · 2014: 27 · 2013: 26 · 2012: 18
- FWCI
- 26.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Leona M. and Harry B. Helmsley Charitable Trust
- European Commission (241883)
- European Foundation for the Study of Diabetes
- Israel Science Foundation (99-2007-71)
- Wolfson Family Charitable Trust (99-2007-71)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- microRNA, pancreatic beta cells, insulin gene expression, DICER1, diabetes mellitus, transcriptional repressor, SOX6, miR-24, miR-26, miR-182, miR-148, islets
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Endoribonucleases, Humans, Immunoenzyme Techniques, Insulin, Luciferases, Repressor Proteins, RNA, Messenger, Transcription, Genetic, Blotting, Western, Down-Regulation, Glucose Intolerance, Mice, Knockout, Integrases, Reverse Transcriptase Polymerase Chain Reaction, MicroRNAs, Ribonuclease III, Insulin-Secreting Cells, Mice, DEAD-box RNA Helicases
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