Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc..
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.
| Errataetall: |
CommentIn: Nat Genet. 2023 Jun;55(6):905-907. - PMID 37291195 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:55 |
|---|---|
| Enthalten in: |
Nature genetics - 55(2023), 6 vom: 07. Juni, Seite 973-983 |
| Sprache: |
Englisch |
|---|
| Links: |
|---|
| Themen: |
Blood Glucose |
|---|
| Anmerkungen: |
Date Completed 14.06.2023 Date Revised 06.03.2024 published: Print-Electronic CommentIn: Nat Genet. 2023 Jun;55(6):905-907. - PMID 37291195 Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41588-023-01408-9 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM357930010 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM357930010 | ||
| 003 | DE-627 | ||
| 005 | 20240306232316.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41588-023-01408-9 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1318.xml |
| 035 | |a (DE-627)NLM357930010 | ||
| 035 | |a (NLM)37291194 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Williamson, Alice |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 14.06.2023 | ||
| 500 | |a Date Revised 06.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Nat Genet. 2023 Jun;55(6):905-907. - PMID 37291195 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s), under exclusive licence to Springer Nature America, Inc. | ||
| 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Insulin |2 NLM | |
| 650 | 7 | |a Glucose |2 NLM | |
| 650 | 7 | |a IY9XDZ35W2 |2 NLM | |
| 650 | 7 | |a Blood Glucose |2 NLM | |
| 700 | 1 | |a Norris, Dougall M |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Xianyong |e verfasserin |4 aut | |
| 700 | 1 | |a Broadaway, K Alaine |e verfasserin |4 aut | |
| 700 | 1 | |a Moxley, Anne H |e verfasserin |4 aut | |
| 700 | 1 | |a Vadlamudi, Swarooparani |e verfasserin |4 aut | |
| 700 | 1 | |a Wilson, Emma P |e verfasserin |4 aut | |
| 700 | 1 | |a Jackson, Anne U |e verfasserin |4 aut | |
| 700 | 1 | |a Ahuja, Vasudha |e verfasserin |4 aut | |
| 700 | 1 | |a Andersen, Mette K |e verfasserin |4 aut | |
| 700 | 1 | |a Arzumanyan, Zorayr |e verfasserin |4 aut | |
| 700 | 1 | |a Bonnycastle, Lori L |e verfasserin |4 aut | |
| 700 | 1 | |a Bornstein, Stefan R |e verfasserin |4 aut | |
| 700 | 1 | |a Bretschneider, Maxi P |e verfasserin |4 aut | |
| 700 | 1 | |a Buchanan, Thomas A |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Yi-Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Chuang, Lee-Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Chung, Ren-Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Clausen, Tine D |e verfasserin |4 aut | |
| 700 | 1 | |a Damm, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Delgado, Graciela E |e verfasserin |4 aut | |
| 700 | 1 | |a de Mello, Vanessa D |e verfasserin |4 aut | |
| 700 | 1 | |a Dupuis, Josée |e verfasserin |4 aut | |
| 700 | 1 | |a Dwivedi, Om P |e verfasserin |4 aut | |
| 700 | 1 | |a Erdos, Michael R |e verfasserin |4 aut | |
| 700 | 1 | |a Fernandes Silva, Lilian |e verfasserin |4 aut | |
| 700 | 1 | |a Frayling, Timothy M |e verfasserin |4 aut | |
| 700 | 1 | |a Gieger, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Goodarzi, Mark O |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Xiuqing |e verfasserin |4 aut | |
| 700 | 1 | |a Gustafsson, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Hakaste, Liisa |e verfasserin |4 aut | |
| 700 | 1 | |a Hammar, Ulf |e verfasserin |4 aut | |
| 700 | 1 | |a Hatem, Gad |e verfasserin |4 aut | |
| 700 | 1 | |a Herrmann, Sandra |e verfasserin |4 aut | |
| 700 | 1 | |a Højlund, Kurt |e verfasserin |4 aut | |
| 700 | 1 | |a Horn, Katrin |e verfasserin |4 aut | |
| 700 | 1 | |a Hsueh, Willa A |e verfasserin |4 aut | |
| 700 | 1 | |a Hung, Yi-Jen |e verfasserin |4 aut | |
| 700 | 1 | |a Hwu, Chii-Min |e verfasserin |4 aut | |
| 700 | 1 | |a Jonsson, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Kårhus, Line L |e verfasserin |4 aut | |
| 700 | 1 | |a Kleber, Marcus E |e verfasserin |4 aut | |
| 700 | 1 | |a Kovacs, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Lakka, Timo A |e verfasserin |4 aut | |
| 700 | 1 | |a Lauzon, Marie |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, I-Te |e verfasserin |4 aut | |
| 700 | 1 | |a Lindgren, Cecilia M |e verfasserin |4 aut | |
| 700 | 1 | |a Lindström, Jaana |e verfasserin |4 aut | |
| 700 | 1 | |a Linneberg, Allan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Ching-Ti |e verfasserin |4 aut | |
| 700 | 1 | |a Luan, Jian'an |e verfasserin |4 aut | |
| 700 | 1 | |a Aly, Dina Mansour |e verfasserin |4 aut | |
| 700 | 1 | |a Mathiesen, Elisabeth |e verfasserin |4 aut | |
| 700 | 1 | |a Moissl, Angela P |e verfasserin |4 aut | |
| 700 | 1 | |a Morris, Andrew P |e verfasserin |4 aut | |
| 700 | 1 | |a Narisu, Narisu |e verfasserin |4 aut | |
| 700 | 1 | |a Perakakis, Nikolaos |e verfasserin |4 aut | |
| 700 | 1 | |a Peters, Annette |e verfasserin |4 aut | |
| 700 | 1 | |a Prasad, Rashmi B |e verfasserin |4 aut | |
| 700 | 1 | |a Rodionov, Roman N |e verfasserin |4 aut | |
| 700 | 1 | |a Roll, Kathryn |e verfasserin |4 aut | |
| 700 | 1 | |a Rundsten, Carsten F |e verfasserin |4 aut | |
| 700 | 1 | |a Sarnowski, Chloé |e verfasserin |4 aut | |
| 700 | 1 | |a Savonen, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Scholz, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Sharma, Sapna |e verfasserin |4 aut | |
| 700 | 1 | |a Stinson, Sara E |e verfasserin |4 aut | |
| 700 | 1 | |a Suleman, Sufyan |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Jingyi |e verfasserin |4 aut | |
| 700 | 1 | |a Taylor, Kent D |e verfasserin |4 aut | |
| 700 | 1 | |a Uusitupa, Matti |e verfasserin |4 aut | |
| 700 | 1 | |a Vistisen, Dorte |e verfasserin |4 aut | |
| 700 | 1 | |a Witte, Daniel R |e verfasserin |4 aut | |
| 700 | 1 | |a Walther, Romy |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Peitao |e verfasserin |4 aut | |
| 700 | 1 | |a Xiang, Anny H |e verfasserin |4 aut | |
| 700 | 1 | |a Zethelius, Björn |e verfasserin |4 aut | |
| 700 | 0 | |a Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC) |e verfasserin |4 aut | |
| 700 | 1 | |a Ahlqvist, Emma |e verfasserin |4 aut | |
| 700 | 1 | |a Bergman, Richard N |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yii-Der Ida |e verfasserin |4 aut | |
| 700 | 1 | |a Collins, Francis S |e verfasserin |4 aut | |
| 700 | 1 | |a Fall, Tove |e verfasserin |4 aut | |
| 700 | 1 | |a Florez, Jose C |e verfasserin |4 aut | |
| 700 | 1 | |a Fritsche, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Grallert, Harald |e verfasserin |4 aut | |
| 700 | 1 | |a Groop, Leif |e verfasserin |4 aut | |
| 700 | 1 | |a Hansen, Torben |e verfasserin |4 aut | |
| 700 | 1 | |a Koistinen, Heikki A |e verfasserin |4 aut | |
| 700 | 1 | |a Komulainen, Pirjo |e verfasserin |4 aut | |
| 700 | 1 | |a Laakso, Markku |e verfasserin |4 aut | |
| 700 | 1 | |a Lind, Lars |e verfasserin |4 aut | |
| 700 | 1 | |a Loeffler, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a März, Winfried |e verfasserin |4 aut | |
| 700 | 1 | |a Meigs, James B |e verfasserin |4 aut | |
| 700 | 1 | |a Raffel, Leslie J |e verfasserin |4 aut | |
| 700 | 1 | |a Rauramaa, Rainer |e verfasserin |4 aut | |
| 700 | 1 | |a Rotter, Jerome I |e verfasserin |4 aut | |
| 700 | 1 | |a Schwarz, Peter E H |e verfasserin |4 aut | |
| 700 | 0 | |a et al |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t Nature genetics |d 1992 |g 55(2023), 6 vom: 07. Juni, Seite 973-983 |w (DE-627)NLM012651230 |x 1546-1718 |7 nnns |
| 773 | 1 | 8 | |g volume:55 |g year:2023 |g number:6 |g day:07 |g month:06 |g pages:973-983 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41588-023-01408-9 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 55 |j 2023 |e 6 |b 07 |c 06 |h 973-983 | ||