Journal Articles

Authors

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
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

Publication Date

6-1-2023

Journal

Nature Genetics

Abstract

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.

Keywords

Humans, Insulin, Genome-Wide Association Study, Insulin Resistance, Diabetes Mellitus, Type 2, Glucose, Blood Glucose

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