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A Central Role for GRB10 in Regulation of Islet Function in Man
Variants in the growth factor receptor-bound protein 10 (GRB10) gene were in a GWAS meta-analysis associated with reduced glucose-stimulated insulin secretion and increased risk of type 2 diabetes (T2D) if inherited from the father, but inexplicably reduced fasting glucose when inherited from the mo...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Public Library of Science
2014
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974640/ https://www.ncbi.nlm.nih.gov/pubmed/24699409 http://dx.doi.org/10.1371/journal.pgen.1004235 |
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| author | Prokopenko, Inga Poon, Wenny Mägi, Reedik Prasad B, Rashmi Salehi, S. Albert Almgren, Peter Osmark, Peter Bouatia-Naji, Nabila Wierup, Nils Fall, Tove Stančáková, Alena Barker, Adam Lagou, Vasiliki Osmond, Clive Xie, Weijia Lahti, Jari Jackson, Anne U. Cheng, Yu-Ching Liu, Jie O'Connell, Jeffrey R. Blomstedt, Paul A. Fadista, Joao Alkayyali, Sami Dayeh, Tasnim Ahlqvist, Emma Taneera, Jalal Lecoeur, Cecile Kumar, Ashish Hansson, Ola Hansson, Karin Voight, Benjamin F. Kang, Hyun Min Levy-Marchal, Claire Vatin, Vincent Palotie, Aarno Syvänen, Ann-Christine Mari, Andrea Weedon, Michael N. Loos, Ruth J. F. Ong, Ken K. Nilsson, Peter Isomaa, Bo Tuomi, Tiinamaija Wareham, Nicholas J. Stumvoll, Michael Widen, Elisabeth Lakka, Timo A. Langenberg, Claudia Tönjes, Anke Rauramaa, Rainer Kuusisto, Johanna Frayling, Timothy M. Froguel, Philippe Walker, Mark Eriksson, Johan G. Ling, Charlotte Kovacs, Peter Ingelsson, Erik McCarthy, Mark I. Shuldiner, Alan R. Silver, Kristi D. Laakso, Markku Groop, Leif Lyssenko, Valeriya |
| author_facet | Prokopenko, Inga Poon, Wenny Mägi, Reedik Prasad B, Rashmi Salehi, S. Albert Almgren, Peter Osmark, Peter Bouatia-Naji, Nabila Wierup, Nils Fall, Tove Stančáková, Alena Barker, Adam Lagou, Vasiliki Osmond, Clive Xie, Weijia Lahti, Jari Jackson, Anne U. Cheng, Yu-Ching Liu, Jie O'Connell, Jeffrey R. Blomstedt, Paul A. Fadista, Joao Alkayyali, Sami Dayeh, Tasnim Ahlqvist, Emma Taneera, Jalal Lecoeur, Cecile Kumar, Ashish Hansson, Ola Hansson, Karin Voight, Benjamin F. Kang, Hyun Min Levy-Marchal, Claire Vatin, Vincent Palotie, Aarno Syvänen, Ann-Christine Mari, Andrea Weedon, Michael N. Loos, Ruth J. F. Ong, Ken K. Nilsson, Peter Isomaa, Bo Tuomi, Tiinamaija Wareham, Nicholas J. Stumvoll, Michael Widen, Elisabeth Lakka, Timo A. Langenberg, Claudia Tönjes, Anke Rauramaa, Rainer Kuusisto, Johanna Frayling, Timothy M. Froguel, Philippe Walker, Mark Eriksson, Johan G. Ling, Charlotte Kovacs, Peter Ingelsson, Erik McCarthy, Mark I. Shuldiner, Alan R. Silver, Kristi D. Laakso, Markku Groop, Leif Lyssenko, Valeriya |
| author_sort | Prokopenko, Inga |
| collection | PubMed |
| description | Variants in the growth factor receptor-bound protein 10 (GRB10) gene were in a GWAS meta-analysis associated with reduced glucose-stimulated insulin secretion and increased risk of type 2 diabetes (T2D) if inherited from the father, but inexplicably reduced fasting glucose when inherited from the mother. GRB10 is a negative regulator of insulin signaling and imprinted in a parent-of-origin fashion in different tissues. GRB10 knock-down in human pancreatic islets showed reduced insulin and glucagon secretion, which together with changes in insulin sensitivity may explain the paradoxical reduction of glucose despite a decrease in insulin secretion. Together, these findings suggest that tissue-specific methylation and possibly imprinting of GRB10 can influence glucose metabolism and contribute to T2D pathogenesis. The data also emphasize the need in genetic studies to consider whether risk alleles are inherited from the mother or the father. |
| format | Online Article Text |
| id | pubmed-3974640 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2014 |
| publisher | Public Library of Science |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-39746402014-04-08 A Central Role for GRB10 in Regulation of Islet Function in Man Prokopenko, Inga Poon, Wenny Mägi, Reedik Prasad B, Rashmi Salehi, S. Albert Almgren, Peter Osmark, Peter Bouatia-Naji, Nabila Wierup, Nils Fall, Tove Stančáková, Alena Barker, Adam Lagou, Vasiliki Osmond, Clive Xie, Weijia Lahti, Jari Jackson, Anne U. Cheng, Yu-Ching Liu, Jie O'Connell, Jeffrey R. Blomstedt, Paul A. Fadista, Joao Alkayyali, Sami Dayeh, Tasnim Ahlqvist, Emma Taneera, Jalal Lecoeur, Cecile Kumar, Ashish Hansson, Ola Hansson, Karin Voight, Benjamin F. Kang, Hyun Min Levy-Marchal, Claire Vatin, Vincent Palotie, Aarno Syvänen, Ann-Christine Mari, Andrea Weedon, Michael N. Loos, Ruth J. F. Ong, Ken K. Nilsson, Peter Isomaa, Bo Tuomi, Tiinamaija Wareham, Nicholas J. Stumvoll, Michael Widen, Elisabeth Lakka, Timo A. Langenberg, Claudia Tönjes, Anke Rauramaa, Rainer Kuusisto, Johanna Frayling, Timothy M. Froguel, Philippe Walker, Mark Eriksson, Johan G. Ling, Charlotte Kovacs, Peter Ingelsson, Erik McCarthy, Mark I. Shuldiner, Alan R. Silver, Kristi D. Laakso, Markku Groop, Leif Lyssenko, Valeriya PLoS Genet Research Article Variants in the growth factor receptor-bound protein 10 (GRB10) gene were in a GWAS meta-analysis associated with reduced glucose-stimulated insulin secretion and increased risk of type 2 diabetes (T2D) if inherited from the father, but inexplicably reduced fasting glucose when inherited from the mother. GRB10 is a negative regulator of insulin signaling and imprinted in a parent-of-origin fashion in different tissues. GRB10 knock-down in human pancreatic islets showed reduced insulin and glucagon secretion, which together with changes in insulin sensitivity may explain the paradoxical reduction of glucose despite a decrease in insulin secretion. Together, these findings suggest that tissue-specific methylation and possibly imprinting of GRB10 can influence glucose metabolism and contribute to T2D pathogenesis. The data also emphasize the need in genetic studies to consider whether risk alleles are inherited from the mother or the father. Public Library of Science 2014-04-03 /pmc/articles/PMC3974640/ /pubmed/24699409 http://dx.doi.org/10.1371/journal.pgen.1004235 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
| spellingShingle | Research Article Prokopenko, Inga Poon, Wenny Mägi, Reedik Prasad B, Rashmi Salehi, S. Albert Almgren, Peter Osmark, Peter Bouatia-Naji, Nabila Wierup, Nils Fall, Tove Stančáková, Alena Barker, Adam Lagou, Vasiliki Osmond, Clive Xie, Weijia Lahti, Jari Jackson, Anne U. Cheng, Yu-Ching Liu, Jie O'Connell, Jeffrey R. Blomstedt, Paul A. Fadista, Joao Alkayyali, Sami Dayeh, Tasnim Ahlqvist, Emma Taneera, Jalal Lecoeur, Cecile Kumar, Ashish Hansson, Ola Hansson, Karin Voight, Benjamin F. Kang, Hyun Min Levy-Marchal, Claire Vatin, Vincent Palotie, Aarno Syvänen, Ann-Christine Mari, Andrea Weedon, Michael N. Loos, Ruth J. F. Ong, Ken K. Nilsson, Peter Isomaa, Bo Tuomi, Tiinamaija Wareham, Nicholas J. Stumvoll, Michael Widen, Elisabeth Lakka, Timo A. Langenberg, Claudia Tönjes, Anke Rauramaa, Rainer Kuusisto, Johanna Frayling, Timothy M. Froguel, Philippe Walker, Mark Eriksson, Johan G. Ling, Charlotte Kovacs, Peter Ingelsson, Erik McCarthy, Mark I. Shuldiner, Alan R. Silver, Kristi D. Laakso, Markku Groop, Leif Lyssenko, Valeriya A Central Role for GRB10 in Regulation of Islet Function in Man |
| title | A Central Role for GRB10 in Regulation of Islet Function in Man |
| title_full | A Central Role for GRB10 in Regulation of Islet Function in Man |
| title_fullStr | A Central Role for GRB10 in Regulation of Islet Function in Man |
| title_full_unstemmed | A Central Role for GRB10 in Regulation of Islet Function in Man |
| title_short | A Central Role for GRB10 in Regulation of Islet Function in Man |
| title_sort | central role for grb10 in regulation of islet function in man |
| topic | Research Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974640/ https://www.ncbi.nlm.nih.gov/pubmed/24699409 http://dx.doi.org/10.1371/journal.pgen.1004235 |
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centralroleforgrb10inregulationofisletfunctioninman |