miRNAs control insulin content in pancreatic β‐cells via downregulation of transcriptional repressors
Abstract 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 m...
Ausführliche Beschreibung
Autor*in: |
Melkman‐Zehavi, Tal [verfasserIn] Oren, Roni [verfasserIn] Kredo‐Russo, Sharon [verfasserIn] Shapira, Tirosh [verfasserIn] Mandelbaum, Amitai D [verfasserIn] Rivkin, Natalia [verfasserIn] Nir, Tomer [verfasserIn] Lennox, Kim A [verfasserIn] Behlke, Mark A [verfasserIn] Dor, Yuval [verfasserIn] Hornstein, Eran [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2011 |
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Schlagwörter: |
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Anmerkung: |
© European Molecular Biology Organization 2011 |
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Übergeordnetes Werk: |
Enthalten in: The EMBO Journal - Nature Publishing Group UK, 2023, 30(2011), 5 vom: 01. Feb., Seite 835-845 |
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Übergeordnetes Werk: |
volume:30 ; year:2011 ; number:5 ; day:01 ; month:02 ; pages:835-845 |
Links: |
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DOI / URN: |
10.1038/emboj.2010.361 |
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Katalog-ID: |
SPR057865981 |
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245 | 1 | 0 | |a miRNAs control insulin content in pancreatic β‐cells via downregulation of transcriptional repressors |
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520 | |a Abstract 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. | ||
520 | |a Abstract A pancreatic β‐cell‐specific knockout of Dicer with a diabetic phenotype reveals critical roles for specific miRNAs in the regulation of insulin expression. | ||
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700 | 1 | |a Oren, Roni |e verfasserin |4 aut | |
700 | 1 | |a Kredo‐Russo, Sharon |e verfasserin |4 aut | |
700 | 1 | |a Shapira, Tirosh |e verfasserin |4 aut | |
700 | 1 | |a Mandelbaum, Amitai D |e verfasserin |4 aut | |
700 | 1 | |a Rivkin, Natalia |e verfasserin |4 aut | |
700 | 1 | |a Nir, Tomer |e verfasserin |4 aut | |
700 | 1 | |a Lennox, Kim A |e verfasserin |4 aut | |
700 | 1 | |a Behlke, Mark A |e verfasserin |4 aut | |
700 | 1 | |a Dor, Yuval |e verfasserin |4 aut | |
700 | 1 | |a Hornstein, Eran |e verfasserin |4 aut | |
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10.1038/emboj.2010.361 doi (DE-627)SPR057865981 (SPR)emboj.2010.361-e DE-627 ger DE-627 rakwb eng Melkman‐Zehavi, Tal verfasserin aut miRNAs control insulin content in pancreatic β‐cells via downregulation of transcriptional repressors 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © European Molecular Biology Organization 2011 Abstract 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. Abstract A pancreatic β‐cell‐specific knockout of Dicer with a diabetic phenotype reveals critical roles for specific miRNAs in the regulation of insulin expression. diabetes (dpeaa)DE-He213 Dicer1 (dpeaa)DE-He213 insulin (dpeaa)DE-He213 miRNA (dpeaa)DE-He213 post‐transcriptional (dpeaa)DE-He213 Oren, Roni verfasserin aut Kredo‐Russo, Sharon verfasserin aut Shapira, Tirosh verfasserin aut Mandelbaum, Amitai D verfasserin aut Rivkin, Natalia verfasserin aut Nir, Tomer verfasserin aut Lennox, Kim A verfasserin aut Behlke, Mark A verfasserin aut Dor, Yuval verfasserin aut Hornstein, Eran verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 30(2011), 5 vom: 01. Feb., Seite 835-845 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:30 year:2011 number:5 day:01 month:02 pages:835-845 https://dx.doi.org/10.1038/emboj.2010.361 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 30 2011 5 01 02 835-845 |
spelling |
10.1038/emboj.2010.361 doi (DE-627)SPR057865981 (SPR)emboj.2010.361-e DE-627 ger DE-627 rakwb eng Melkman‐Zehavi, Tal verfasserin aut miRNAs control insulin content in pancreatic β‐cells via downregulation of transcriptional repressors 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © European Molecular Biology Organization 2011 Abstract 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. Abstract A pancreatic β‐cell‐specific knockout of Dicer with a diabetic phenotype reveals critical roles for specific miRNAs in the regulation of insulin expression. diabetes (dpeaa)DE-He213 Dicer1 (dpeaa)DE-He213 insulin (dpeaa)DE-He213 miRNA (dpeaa)DE-He213 post‐transcriptional (dpeaa)DE-He213 Oren, Roni verfasserin aut Kredo‐Russo, Sharon verfasserin aut Shapira, Tirosh verfasserin aut Mandelbaum, Amitai D verfasserin aut Rivkin, Natalia verfasserin aut Nir, Tomer verfasserin aut Lennox, Kim A verfasserin aut Behlke, Mark A verfasserin aut Dor, Yuval verfasserin aut Hornstein, Eran verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 30(2011), 5 vom: 01. Feb., Seite 835-845 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:30 year:2011 number:5 day:01 month:02 pages:835-845 https://dx.doi.org/10.1038/emboj.2010.361 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 30 2011 5 01 02 835-845 |
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10.1038/emboj.2010.361 doi (DE-627)SPR057865981 (SPR)emboj.2010.361-e DE-627 ger DE-627 rakwb eng Melkman‐Zehavi, Tal verfasserin aut miRNAs control insulin content in pancreatic β‐cells via downregulation of transcriptional repressors 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © European Molecular Biology Organization 2011 Abstract 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. Abstract A pancreatic β‐cell‐specific knockout of Dicer with a diabetic phenotype reveals critical roles for specific miRNAs in the regulation of insulin expression. diabetes (dpeaa)DE-He213 Dicer1 (dpeaa)DE-He213 insulin (dpeaa)DE-He213 miRNA (dpeaa)DE-He213 post‐transcriptional (dpeaa)DE-He213 Oren, Roni verfasserin aut Kredo‐Russo, Sharon verfasserin aut Shapira, Tirosh verfasserin aut Mandelbaum, Amitai D verfasserin aut Rivkin, Natalia verfasserin aut Nir, Tomer verfasserin aut Lennox, Kim A verfasserin aut Behlke, Mark A verfasserin aut Dor, Yuval verfasserin aut Hornstein, Eran verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 30(2011), 5 vom: 01. Feb., Seite 835-845 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:30 year:2011 number:5 day:01 month:02 pages:835-845 https://dx.doi.org/10.1038/emboj.2010.361 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 30 2011 5 01 02 835-845 |
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10.1038/emboj.2010.361 doi (DE-627)SPR057865981 (SPR)emboj.2010.361-e DE-627 ger DE-627 rakwb eng Melkman‐Zehavi, Tal verfasserin aut miRNAs control insulin content in pancreatic β‐cells via downregulation of transcriptional repressors 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © European Molecular Biology Organization 2011 Abstract 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. Abstract A pancreatic β‐cell‐specific knockout of Dicer with a diabetic phenotype reveals critical roles for specific miRNAs in the regulation of insulin expression. diabetes (dpeaa)DE-He213 Dicer1 (dpeaa)DE-He213 insulin (dpeaa)DE-He213 miRNA (dpeaa)DE-He213 post‐transcriptional (dpeaa)DE-He213 Oren, Roni verfasserin aut Kredo‐Russo, Sharon verfasserin aut Shapira, Tirosh verfasserin aut Mandelbaum, Amitai D verfasserin aut Rivkin, Natalia verfasserin aut Nir, Tomer verfasserin aut Lennox, Kim A verfasserin aut Behlke, Mark A verfasserin aut Dor, Yuval verfasserin aut Hornstein, Eran verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 30(2011), 5 vom: 01. Feb., Seite 835-845 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:30 year:2011 number:5 day:01 month:02 pages:835-845 https://dx.doi.org/10.1038/emboj.2010.361 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 30 2011 5 01 02 835-845 |
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10.1038/emboj.2010.361 doi (DE-627)SPR057865981 (SPR)emboj.2010.361-e DE-627 ger DE-627 rakwb eng Melkman‐Zehavi, Tal verfasserin aut miRNAs control insulin content in pancreatic β‐cells via downregulation of transcriptional repressors 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © European Molecular Biology Organization 2011 Abstract 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. Abstract A pancreatic β‐cell‐specific knockout of Dicer with a diabetic phenotype reveals critical roles for specific miRNAs in the regulation of insulin expression. diabetes (dpeaa)DE-He213 Dicer1 (dpeaa)DE-He213 insulin (dpeaa)DE-He213 miRNA (dpeaa)DE-He213 post‐transcriptional (dpeaa)DE-He213 Oren, Roni verfasserin aut Kredo‐Russo, Sharon verfasserin aut Shapira, Tirosh verfasserin aut Mandelbaum, Amitai D verfasserin aut Rivkin, Natalia verfasserin aut Nir, Tomer verfasserin aut Lennox, Kim A verfasserin aut Behlke, Mark A verfasserin aut Dor, Yuval verfasserin aut Hornstein, Eran verfasserin aut Enthalten in The EMBO Journal Nature Publishing Group UK, 2023 30(2011), 5 vom: 01. Feb., Seite 835-845 (DE-627)266022529 (DE-600)1467419-1 1460-2075 nnns volume:30 year:2011 number:5 day:01 month:02 pages:835-845 https://dx.doi.org/10.1038/emboj.2010.361 X:SPRINGER Resolving-System lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 30 2011 5 01 02 835-845 |
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Enthalten in The EMBO Journal 30(2011), 5 vom: 01. Feb., Seite 835-845 volume:30 year:2011 number:5 day:01 month:02 pages:835-845 |
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diabetes Dicer1 insulin miRNA post‐transcriptional |
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Melkman‐Zehavi, Tal @@aut@@ Oren, Roni @@aut@@ Kredo‐Russo, Sharon @@aut@@ Shapira, Tirosh @@aut@@ Mandelbaum, Amitai D @@aut@@ Rivkin, Natalia @@aut@@ Nir, Tomer @@aut@@ Lennox, Kim A @@aut@@ Behlke, Mark A @@aut@@ Dor, Yuval @@aut@@ Hornstein, Eran @@aut@@ |
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Melkman‐Zehavi, Tal |
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Melkman‐Zehavi, Tal misc diabetes misc Dicer1 misc insulin misc miRNA misc post‐transcriptional miRNAs control insulin content in pancreatic β‐cells via downregulation of transcriptional repressors |
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miRNAs control insulin content in pancreatic β‐cells via downregulation of transcriptional repressors diabetes (dpeaa)DE-He213 Dicer1 (dpeaa)DE-He213 insulin (dpeaa)DE-He213 miRNA (dpeaa)DE-He213 post‐transcriptional (dpeaa)DE-He213 |
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misc diabetes misc Dicer1 misc insulin misc miRNA misc post‐transcriptional |
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miRNAs control insulin content in pancreatic β‐cells via downregulation of transcriptional repressors |
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miRNAs control insulin content in pancreatic β‐cells via downregulation of transcriptional repressors |
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Melkman‐Zehavi, Tal Oren, Roni Kredo‐Russo, Sharon Shapira, Tirosh Mandelbaum, Amitai D Rivkin, Natalia Nir, Tomer Lennox, Kim A Behlke, Mark A Dor, Yuval Hornstein, Eran |
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mirnas control insulin content in pancreatic β‐cells via downregulation of transcriptional repressors |
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miRNAs control insulin content in pancreatic β‐cells via downregulation of transcriptional repressors |
abstract |
Abstract 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. Abstract A pancreatic β‐cell‐specific knockout of Dicer with a diabetic phenotype reveals critical roles for specific miRNAs in the regulation of insulin expression. © European Molecular Biology Organization 2011 |
abstractGer |
Abstract 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. Abstract A pancreatic β‐cell‐specific knockout of Dicer with a diabetic phenotype reveals critical roles for specific miRNAs in the regulation of insulin expression. © European Molecular Biology Organization 2011 |
abstract_unstemmed |
Abstract 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. Abstract A pancreatic β‐cell‐specific knockout of Dicer with a diabetic phenotype reveals critical roles for specific miRNAs in the regulation of insulin expression. © European Molecular Biology Organization 2011 |
collection_details |
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container_issue |
5 |
title_short |
miRNAs control insulin content in pancreatic β‐cells via downregulation of transcriptional repressors |
url |
https://dx.doi.org/10.1038/emboj.2010.361 |
remote_bool |
true |
author2 |
Oren, Roni Kredo‐Russo, Sharon Shapira, Tirosh Mandelbaum, Amitai D Rivkin, Natalia Nir, Tomer Lennox, Kim A Behlke, Mark A Dor, Yuval Hornstein, Eran |
author2Str |
Oren, Roni Kredo‐Russo, Sharon Shapira, Tirosh Mandelbaum, Amitai D Rivkin, Natalia Nir, Tomer Lennox, Kim A Behlke, Mark A Dor, Yuval Hornstein, Eran |
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hochschulschrift_bool |
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doi_str |
10.1038/emboj.2010.361 |
up_date |
2024-10-18T04:52:34.808Z |
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|
score |
7.400717 |