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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake: article

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h af...

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Hauptverfasser: Williamson, Alice M. (VerfasserIn) , Norris, Dougall M. (VerfasserIn) , Yin, Xianyong (VerfasserIn) , Broadaway, K. Alaine (VerfasserIn) , Moxley, Anne H. (VerfasserIn) , Vadlamudi, Swarooparani (VerfasserIn) , Wilson, Emma P. (VerfasserIn) , Jackson, Anne U. (VerfasserIn) , Ahuja, Vasudha (VerfasserIn) , Andersen, Mette K. (VerfasserIn) , Arzumanyan, Zorayr (VerfasserIn) , Bonnycastle, Lori L. (VerfasserIn) , Bornstein, Stefan R. (VerfasserIn) , Bretschneider, Maxi P. (VerfasserIn) , Buchanan, Thomas A. (VerfasserIn) , Chang, Yi-Cheng (VerfasserIn) , Chuang, Lee-Ming (VerfasserIn) , Chung, Ren-Hua (VerfasserIn) , Clausen, Tine D. (VerfasserIn) , Damm, Peter (VerfasserIn) , Delgado Gonzales de Kleber, Graciela (VerfasserIn) , de Mello, Vanessa D. (VerfasserIn) , Dupuis, Josée (VerfasserIn) , Dwivedi, Om P. (VerfasserIn) , Erdos, Michael R. (VerfasserIn) , Silva, Lilian Fernandes (VerfasserIn) , Frayling, Timothy M. (VerfasserIn) , Gieger, Christian (VerfasserIn) , Goodarzi, Mark O. (VerfasserIn) , Guo, Xiuqing (VerfasserIn) , Gustafsson, Stefan (VerfasserIn) , Hakaste, Liisa (VerfasserIn) , Hammar, Ulf (VerfasserIn) , Hatem, Gad (VerfasserIn) , Herrmann, Sandra (VerfasserIn) , Højlund, Kurt (VerfasserIn) , Horn, Katrin (VerfasserIn) , Hsueh, Willa A. (VerfasserIn) , Hung, Yi-Jen (VerfasserIn) , Hwu, Chii-Min (VerfasserIn) , Jonsson, Anna (VerfasserIn) , Kårhus, Line L. (VerfasserIn) , Kleber, Marcus E. (VerfasserIn) , Kovacs, Peter (VerfasserIn) , Lakka, Timo A. (VerfasserIn) , Lauzon, Marie (VerfasserIn) , Lee, I.-Te (VerfasserIn) , Lindgren, Cecilia M. (VerfasserIn) , Lindström, Jaana (VerfasserIn) , Linneberg, Allan (VerfasserIn) , Liu, Ching-Ti (VerfasserIn) , Luan, Jian’an (VerfasserIn) , Aly, Dina Mansour (VerfasserIn) , Mathiesen, Elisabeth (VerfasserIn) , Moissl-Blanke, Angela P. (VerfasserIn) , Morris, Andrew P. (VerfasserIn) , Narisu, Narisu (VerfasserIn) , Perakakis, Nikolaos (VerfasserIn) , Peters, Annette (VerfasserIn) , Prasad, Rashmi B. (VerfasserIn) , Rodionov, Roman N. (VerfasserIn) , Roll, Kathryn (VerfasserIn) , Rundsten, Carsten F. (VerfasserIn) , Sarnowski, Chloé (VerfasserIn) , Savonen, Kai (VerfasserIn) , Scholz, Markus (VerfasserIn) , Sharma, Sapna (VerfasserIn) , Stinson, Sara E. (VerfasserIn) , Suleman, Sufyan (VerfasserIn) , Tan, Jingyi (VerfasserIn) , Taylor, Kent D. (VerfasserIn) , Uusitupa, Matti (VerfasserIn) , Vistisen, Dorte (VerfasserIn) , Witte, Daniel R. (VerfasserIn) , Walther, Romy (VerfasserIn) , Wu, Peitao (VerfasserIn) , Xiang, Anny H. (VerfasserIn) , Zethelius, Björn (VerfasserIn) , Ahlqvist, Emma (VerfasserIn) , Bergman, Richard N. (VerfasserIn) , Chen, Yii-Der Ida (VerfasserIn) , Collins, Francis S. (VerfasserIn) , Fall, Tove (VerfasserIn) , Florez, Jose C. (VerfasserIn) , Fritsche, Andreas (VerfasserIn) , Grallert, Harald (VerfasserIn) , Groop, Leif (VerfasserIn) , Hansen, Torben (VerfasserIn) , Koistinen, Heikki A. (VerfasserIn) , Komulainen, Pirjo (VerfasserIn) , Laakso, Markku (VerfasserIn) , Lind, Lars (VerfasserIn) , Loeffler, Markus (VerfasserIn) , März, Winfried (VerfasserIn) , Meigs, James B. (VerfasserIn) , Raffel, Leslie J. (VerfasserIn) , Rauramaa, Rainer (VerfasserIn) , Rotter, Jerome I. (VerfasserIn) , Schwarz, Peter E. H. (VerfasserIn) , Stumvoll, Michael (VerfasserIn) , Sundström, Johan (VerfasserIn) , Tönjes, Anke (VerfasserIn) , Tuomi, Tiinamaija (VerfasserIn) , Tuomilehto, Jaakko (VerfasserIn) , Wagner, Róbert (VerfasserIn) , Barroso, Inês (VerfasserIn) , Walker, Mark (VerfasserIn) , Grarup, Niels (VerfasserIn) , Boehnke, Michael (VerfasserIn) , Wareham, Nicholas J. (VerfasserIn) , Mohlke, Karen L. (VerfasserIn) , Wheeler, Eleanor (VerfasserIn) , O’Rahilly, Stephen (VerfasserIn) , Fazakerley, Daniel J. (VerfasserIn) , Langenberg, Claudia (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: June 2023
In: Nature genetics
Year: 2023, Jahrgang: 55, Heft: 6, Pages: 973-983
ISSN:1546-1718
DOI:10.1038/s41588-023-01408-9
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41588-023-01408-9
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41588-023-01408-9
Volltext
Verfasserangaben:Alice Williamson, Dougall M. Norris, Xianyong Yin, K. Alaine Broadaway, Anne H. Moxley, Swarooparani Vadlamudi, Emma P. Wilson, Anne U. Jackson, Vasudha Ahuja, Mette K. Andersen, Zorayr Arzumanyan, Lori L. Bonnycastle, Stefan R. Bornstein, Maxi P. Bretschneider, Thomas A. Buchanan, Yi-Cheng Chang, Lee-Ming Chuang, Ren-Hua Chung, Tine D. Clausen, Peter Damm, Graciela E. Delgado, Vanessa D. de Mello, Josée Dupuis, Om P. Dwivedi, Michael R. Erdos, Lilian Fernandes Silva, Timothy M. Frayling, Christian Gieger, Mark O. Goodarzi, Xiuqing Guo, Stefan Gustafsson, Liisa Hakaste, Ulf Hammar, Gad Hatem, Sandra Herrmann, Kurt Højlund, Katrin Horn, Willa A. Hsueh, Yi-Jen Hung, Chii-Min Hwu, Anna Jonsson, Line L. Kårhus, Marcus E. Kleber, Peter Kovacs, Timo A. Lakka, Marie Lauzon, I.-Te Lee, Cecilia M. Lindgren, Jaana Lindström, Allan Linneberg, Ching-Ti Liu, Jian’an Luan, Dina Mansour Aly, Elisabeth Mathiesen, Angela P. Moissl, Andrew P. Morris, Narisu Narisu, Nikolaos Perakakis, Annette Peters, Rashmi B. Prasad, Roman N. Rodionov, Kathryn Roll, Carsten F. Rundsten, Chloé Sarnowski, Kai Savonen, Markus Scholz, Sapna Sharma, Sara E. Stinson, Sufyan Suleman, Jingyi Tan, Kent D. Taylor, Matti Uusitupa, Dorte Vistisen, Daniel R. Witte, Romy Walther, Peitao Wu, Anny H. Xiang, Björn Zethelius, Vanessa D. de Mello, Emma Ahlqvist, Richard N. Bergman, Yii-Der Ida Chen, Francis S. Collins, Tove Fall, Jose C. Florez, Andreas Fritsche, Harald Grallert, Leif Groop, Torben Hansen, Heikki A. Koistinen, Pirjo Komulainen, Markku Laakso, Lars Lind, Markus Loeffler, Winfried März, James B. Meigs, Leslie J. Raffel, Rainer Rauramaa, Jerome I. Rotter, Peter E. H. Schwarz, Michael Stumvoll, Johan Sundström, Anke Tönjes, Tiinamaija Tuomi, Jaakko Tuomilehto, Robert Wagner, Inês Barroso, Mark Walker, Niels Grarup, Michael Boehnke, Nicholas J. Wareham, Karen L. Mohlke, Eleanor Wheeler, Stephen O’Rahilly, Daniel J. Fazakerley & Claudia Langenberg

MARC

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245 1 0 |a Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake  |b article  |c Alice Williamson, Dougall M. Norris, Xianyong Yin, K. Alaine Broadaway, Anne H. Moxley, Swarooparani Vadlamudi, Emma P. Wilson, Anne U. Jackson, Vasudha Ahuja, Mette K. Andersen, Zorayr Arzumanyan, Lori L. Bonnycastle, Stefan R. Bornstein, Maxi P. Bretschneider, Thomas A. Buchanan, Yi-Cheng Chang, Lee-Ming Chuang, Ren-Hua Chung, Tine D. Clausen, Peter Damm, Graciela E. Delgado, Vanessa D. de Mello, Josée Dupuis, Om P. Dwivedi, Michael R. Erdos, Lilian Fernandes Silva, Timothy M. Frayling, Christian Gieger, Mark O. Goodarzi, Xiuqing Guo, Stefan Gustafsson, Liisa Hakaste, Ulf Hammar, Gad Hatem, Sandra Herrmann, Kurt Højlund, Katrin Horn, Willa A. Hsueh, Yi-Jen Hung, Chii-Min Hwu, Anna Jonsson, Line L. Kårhus, Marcus E. Kleber, Peter Kovacs, Timo A. Lakka, Marie Lauzon, I.-Te Lee, Cecilia M. Lindgren, Jaana Lindström, Allan Linneberg, Ching-Ti Liu, Jian’an Luan, Dina Mansour Aly, Elisabeth Mathiesen, Angela P. Moissl, Andrew P. Morris, Narisu Narisu, Nikolaos Perakakis, Annette Peters, Rashmi B. Prasad, Roman N. Rodionov, Kathryn Roll, Carsten F. Rundsten, Chloé Sarnowski, Kai Savonen, Markus Scholz, Sapna Sharma, Sara E. Stinson, Sufyan Suleman, Jingyi Tan, Kent D. Taylor, Matti Uusitupa, Dorte Vistisen, Daniel R. Witte, Romy Walther, Peitao Wu, Anny H. Xiang, Björn Zethelius, Vanessa D. de Mello, Emma Ahlqvist, Richard N. Bergman, Yii-Der Ida Chen, Francis S. Collins, Tove Fall, Jose C. Florez, Andreas Fritsche, Harald Grallert, Leif Groop, Torben Hansen, Heikki A. Koistinen, Pirjo Komulainen, Markku Laakso, Lars Lind, Markus Loeffler, Winfried März, James B. Meigs, Leslie J. Raffel, Rainer Rauramaa, Jerome I. Rotter, Peter E. H. Schwarz, Michael Stumvoll, Johan Sundström, Anke Tönjes, Tiinamaija Tuomi, Jaakko Tuomilehto, Robert Wagner, Inês Barroso, Mark Walker, Niels Grarup, Michael Boehnke, Nicholas J. Wareham, Karen L. Mohlke, Eleanor Wheeler, Stephen O’Rahilly, Daniel J. Fazakerley & Claudia Langenberg 
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520 |a Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10−8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits. 
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JSO |a {"title":[{"title_sort":"Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake","subtitle":"article","title":"Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake"}],"relHost":[{"part":{"volume":"55","extent":"32","year":"2023","pages":"973-983","issue":"6","text":"55(2023), 6 vom: Juni, Seite 973-983"},"pubHistory":["1.1992 -"],"id":{"eki":["303393734"],"zdb":["1494946-5"],"issn":["1546-1718"]},"type":{"bibl":"periodical","media":"Online-Ressource"},"titleAlt":[{"title":"Genetics"}],"recId":"303393734","origin":[{"dateIssuedDisp":"1992-","publisher":"Macmillan Publishers Limited, part of Springer Nature ; Nature America","publisherPlace":"London ; New York, NY","dateIssuedKey":"1992"}],"language":["eng"],"title":[{"title":"Nature genetics","title_sort":"Nature genetics"}],"physDesc":[{"extent":"Online-Ressource"}],"disp":"Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake articleNature genetics","note":["Gesehen am 02.03.05"]}],"physDesc":[{"extent":"32 S.","noteIll":"Illustrationen"}],"id":{"eki":["1881605671"],"doi":["10.1038/s41588-023-01408-9"]},"type":{"media":"Online-Ressource","bibl":"article-journal"},"language":["eng"],"person":[{"display":"Williamson, Alice M.","role":"aut","family":"Williamson","given":"Alice M."},{"role":"aut","display":"Norris, Dougall M.","given":"Dougall M.","family":"Norris"},{"display":"Yin, Xianyong","role":"aut","family":"Yin","given":"Xianyong"},{"family":"Broadaway","given":"K. 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SRT |a WILLIAMSONGENOMEWIDE2023 

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