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...
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Public Library of Science (PLoS)
2014-04-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1004235 |
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| author | Inga Prokopenko Wenny Poon Reedik Mägi Rashmi Prasad B S Albert Salehi Peter Almgren Peter Osmark Nabila Bouatia-Naji Nils Wierup Tove Fall Alena Stančáková Adam Barker Vasiliki Lagou Clive Osmond Weijia Xie Jari Lahti Anne U Jackson Yu-Ching Cheng Jie Liu Jeffrey R O'Connell Paul A Blomstedt Joao Fadista Joao Fadista Sami Alkayyali Tasnim Dayeh Emma Ahlqvist Jalal Taneera Cecile Lecoeur Ashish Kumar Ola Hansson Karin Hansson Benjamin F Voight Hyun Min Kang Claire Levy-Marchal Vincent Vatin Aarno Palotie Ann-Christine Syvänen Andrea Mari Michael N Weedon Ruth J F Loos Ken K Ong Peter Nilsson Bo Isomaa Tiinamaija Tuomi Nicholas J Wareham Michael Stumvoll Elisabeth Widen Timo A Lakka Claudia Langenberg Anke Tönjes Rainer Rauramaa Johanna Kuusisto Timothy M Frayling Philippe Froguel Mark Walker Johan G Eriksson Charlotte Ling Peter Kovacs Erik Ingelsson Mark I McCarthy Alan R Shuldiner Kristi D Silver Markku Laakso Leif Groop Valeriya Lyssenko |
| author_facet | Inga Prokopenko Wenny Poon Reedik Mägi Rashmi Prasad B S Albert Salehi Peter Almgren Peter Osmark Nabila Bouatia-Naji Nils Wierup Tove Fall Alena Stančáková Adam Barker Vasiliki Lagou Clive Osmond Weijia Xie Jari Lahti Anne U Jackson Yu-Ching Cheng Jie Liu Jeffrey R O'Connell Paul A Blomstedt Joao Fadista Joao Fadista Sami Alkayyali Tasnim Dayeh Emma Ahlqvist Jalal Taneera Cecile Lecoeur Ashish Kumar Ola Hansson Karin Hansson Benjamin F Voight Hyun Min Kang Claire Levy-Marchal Vincent Vatin Aarno Palotie Ann-Christine Syvänen Andrea Mari Michael N Weedon Ruth J F Loos Ken K Ong Peter Nilsson Bo Isomaa Tiinamaija Tuomi Nicholas J Wareham Michael Stumvoll Elisabeth Widen Timo A Lakka Claudia Langenberg Anke Tönjes Rainer Rauramaa Johanna Kuusisto Timothy M Frayling Philippe Froguel Mark Walker Johan G Eriksson Charlotte Ling Peter Kovacs Erik Ingelsson Mark I McCarthy Alan R Shuldiner Kristi D Silver Markku Laakso Leif Groop Valeriya Lyssenko |
| author_sort | Inga Prokopenko |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-426bbcbc38894f88b836facbc9420ecc |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2014-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-426bbcbc38894f88b836facbc9420ecc2025-08-20T02:22:49ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-04-01104e100423510.1371/journal.pgen.1004235A central role for GRB10 in regulation of islet function in man.Inga ProkopenkoWenny PoonReedik MägiRashmi Prasad BS Albert SalehiPeter AlmgrenPeter OsmarkNabila Bouatia-NajiNils WierupTove FallAlena StančákováAdam BarkerVasiliki LagouClive OsmondWeijia XieJari LahtiAnne U JacksonYu-Ching ChengJie LiuJeffrey R O'ConnellPaul A BlomstedtJoao FadistaJoao FadistaSami AlkayyaliTasnim DayehEmma AhlqvistJalal TaneeraCecile LecoeurAshish KumarOla HanssonKarin HanssonBenjamin F VoightHyun Min KangClaire Levy-MarchalVincent VatinAarno PalotieAnn-Christine SyvänenAndrea MariMichael N WeedonRuth J F LoosKen K OngPeter NilssonBo IsomaaTiinamaija TuomiNicholas J WarehamMichael StumvollElisabeth WidenTimo A LakkaClaudia LangenbergAnke TönjesRainer RauramaaJohanna KuusistoTimothy M FraylingPhilippe FroguelMark WalkerJohan G ErikssonCharlotte LingPeter KovacsErik IngelssonMark I McCarthyAlan R ShuldinerKristi D SilverMarkku LaaksoLeif GroopValeriya LyssenkoVariants 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.https://doi.org/10.1371/journal.pgen.1004235 |
| spellingShingle | Inga Prokopenko Wenny Poon Reedik Mägi Rashmi Prasad B S Albert Salehi Peter Almgren Peter Osmark Nabila Bouatia-Naji Nils Wierup Tove Fall Alena Stančáková Adam Barker Vasiliki Lagou Clive Osmond Weijia Xie Jari Lahti Anne U Jackson Yu-Ching Cheng Jie Liu Jeffrey R O'Connell Paul A Blomstedt Joao Fadista Joao Fadista Sami Alkayyali Tasnim Dayeh Emma Ahlqvist Jalal Taneera Cecile Lecoeur Ashish Kumar Ola Hansson Karin Hansson Benjamin F Voight Hyun Min Kang Claire Levy-Marchal Vincent Vatin Aarno Palotie Ann-Christine Syvänen Andrea Mari Michael N Weedon Ruth J F Loos Ken K Ong Peter Nilsson Bo Isomaa Tiinamaija Tuomi Nicholas J Wareham Michael Stumvoll Elisabeth Widen Timo A Lakka Claudia Langenberg Anke Tönjes Rainer Rauramaa Johanna Kuusisto Timothy M Frayling Philippe Froguel Mark Walker Johan G Eriksson Charlotte Ling Peter Kovacs Erik Ingelsson Mark I McCarthy Alan R Shuldiner Kristi D Silver Markku Laakso Leif Groop Valeriya Lyssenko A central role for GRB10 in regulation of islet function in man. PLoS Genetics |
| 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 |
| url | https://doi.org/10.1371/journal.pgen.1004235 |
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