標題: | Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake |
作者: | Williamson, Alice Norris, Dougall M Yin, Xianyong Broadaway, K Alaine Moxley, Anne H Vadlamudi, Swarooparani Wilson, Emma P Jackson, Anne U Ahuja, Vasudha Andersen, Mette K Arzumanyan, Zorayr Bonnycastle, Lori L Bornstein, Stefan R Bretschneider, Maxi P Buchanan, Thomas A YI-CHENG CHANG LEE-MING CHUANG Chung, Ren-Hua Clausen, Tine D Damm, Peter Delgado, Graciela E de Mello, Vanessa D Dupuis, Josée Dwivedi, Om P Erdos, Michael R Silva, Lilian Fernandes Frayling, Timothy M Gieger, Christian Goodarzi, Mark O Guo, Xiuqing Gustafsson, Stefan Hakaste, Liisa Hammar, Ulf Hatem, Gad Herrmann, Sandra Højlund, Kurt Horn, Katrin Hsueh, Willa A Hung, Yi-Jen Hwu, Chii-Min Jonsson, Anna Kårhus, Line L Kleber, Marcus E Kovacs, Peter Lakka, Timo A Lauzon, Marie Lee, I-Te Lindgren, Cecilia M Lindström, Jaana Linneberg, Allan Liu, Ching-Ti Luan, Jian'an Aly, Dina Mansour Mathiesen, Elisabeth Moissl, Angela P Morris, Andrew P Narisu, Narisu Perakakis, Nikolaos Peters, Annette Prasad, Rashmi B Rodionov, Roman N Roll, Kathryn Rundsten, Carsten F Sarnowski, Chloé Savonen, Kai Scholz, Markus Sharma, Sapna Stinson, Sara E Suleman, Sufyan Tan, Jingyi Taylor, Kent D Uusitupa, Matti Vistisen, Dorte Witte, Daniel R Walther, Romy Wu, Peitao Xiang, Anny H Zethelius, Björn Ahlqvist, Emma Bergman, Richard N Chen, Yii-Der Ida Collins, Francis S Fall, Tove Florez, Jose C Fritsche, Andreas Grallert, Harald Groop, Leif Hansen, Torben Koistinen, Heikki A Komulainen, Pirjo Laakso, Markku Lind, Lars Loeffler, Markus März, Winfried Meigs, James B Raffel, Leslie J Rauramaa, Rainer Rotter, Jerome I Schwarz, Peter E H Stumvoll, Michael Sundström, Johan Tönjes, Anke Tuomi, Tiinamaija Tuomilehto, Jaakko Wagner, Robert Barroso, Inês Walker, Mark Grarup, Niels Boehnke, Michael Wareham, Nicholas J Mohlke, Karen L Wheeler, Eleanor O'Rahilly, Stephen Fazakerley, Daniel J Langenberg, Claudia |
公開日期: | 六月-2023 |
卷: | 55 |
期: | 6 |
來源出版物: | Nature genetics |
摘要: | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/633800 |
ISSN: | 1061-4036 1546-1718 |
DOI: | 10.1038/s41588-023-01408-9 |
顯示於: | 醫學系
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