A Central Role for GRB10 in Regulation of Islet Function in Man

Inga Prokopenko; Wenny Poon; Reedik Maegi; Rashmi B. Prasad; S. Albert Salehi; Peter Almgren; Peter Osmark; Nabila Bouatia-Naji; Nils Wierup; Tove Fall; Alena Stancakova; 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; 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 Syvanen; 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 Tonjes; 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

doi:10.1371/journal.pgen.1004235

Back

A Central Role for GRB10 in Regulation of Islet Function in Man

Journal article

Open access

Peer reviewed

A Central Role for GRB10 in Regulation of Islet Function in Man

Inga Prokopenko, Wenny Poon, Reedik Maegi, Rashmi B. Prasad, S. Albert Salehi, Peter Almgren, Peter Osmark, Nabila Bouatia-Naji, Nils Wierup, Tove Fall, …

PLoS genetics, Vol.10(4), pp.e1004235-e1004235

01/04/2014

DOI: https://doi.org/10.1371/journal.pgen.1004235

PMID: 24699409

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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.

Files and links (1)

url

https://doi.org/10.1371/journal.pgen.1004235View

Published (Version of record) Open

Metrics

1 Record Views

130 Times Cited - Web of Science

See more details

Details

Title: A Central Role for GRB10 in Regulation of Islet Function in Man
Creators: Inga Prokopenko - Hammersmith Hospital
Wenny Poon - Lund University
Reedik Maegi - University of Oxford
Rashmi B. Prasad - Lund University
S. Albert Salehi - Lund University
Peter Almgren - Lund University
Peter Osmark - Lund University
Nabila Bouatia-Naji - Université de Lille
Nils Wierup - Lund University
Tove Fall - Science for Life Laboratory
Alena Stancakova - University of Eastern Finland
Adam Barker - MRC Epidemiology Unit
Vasiliki Lagou - Oxford Centre for Diabetes, Endocrinology and Metabolism
Clive Osmond - MRC Lifecourse Epidemiology Unit
Weijia Xie - University of Exeter
Jari Lahti - University of Helsinki
Anne U. Jackson - University of Michigan–Ann Arbor
Yu-Ching Cheng - University of Maryland, Baltimore
Jie Liu - University of Maryland, Baltimore
Jeffrey R. O'Connell - Supreme Council Of Health
Paul A. Blomstedt - Åbo Akademi University
Joao Fadista - Lund University
Sami Alkayyali - Lund University
Tasnim Dayeh - Scania
Emma Ahlqvist - Lund University
Jalal Taneera - Lund University
Cecile Lecoeur - Université de Lille
Ashish Kumar - University of Oxford
Ola Hansson - Lund University
Karin Hansson - Lund University
Benjamin F. Voight - University of Pennsylvania
Hyun Min Kang - University of Michigan–Ann Arbor
Claire Levy-Marchal - Inserm
Vincent Vatin - Institut Pasteur de Lille
Aarno Palotie - Institute for Molecular Medicine Finland
Ann-Christine Syvanen - Uppsala University
Andrea Mari - CNR, Inst Biomed Engn, Padua, Italy
Michael N. Weedon - University of Exeter
Ruth J. F. Loos - MRC Epidemiology Unit
Ken K. Ong - University of Cambridge
Peter Nilsson - Skåne University Hospital
Bo Isomaa - Folkhälsans Forskningscentrum
Tiinamaija Tuomi - Folkhalsan Res Ctr, Helsinki, Finland
Nicholas J. Wareham - MRC Epidemiology Unit
Michael Stumvoll - Leipzig University
Elisabeth Widen - Institute for Molecular Medicine Finland
Timo A. Lakka - University of Eastern Finland
Claudia Langenberg - MRC Epidemiology Unit
Anke Tonjes - IFB Adiposity Diseases
Rainer Rauramaa - University of Eastern Finland
Johanna Kuusisto - University of Eastern Finland
Timothy M. Frayling - University of Exeter
Philippe Froguel - Imperial College London
Mark Walker - Newcastle University
Johan G. Eriksson - Helsinki University Hospital
Charlotte Ling - Scania
Peter Kovacs - Leipzig University
Erik Ingelsson - Science for Life Laboratory
Mark I. McCarthy - Oxford Centre for Diabetes, Endocrinology and Metabolism
Alan R. Shuldiner - University of Maryland, Baltimore
Kristi D. Silver - University of Maryland, Baltimore
Markku Laakso - Kuopio University Hospital
Leif Groop - University of Helsinki
Valeriya Lyssenko - Lund University
Publication Details: PLoS genetics, Vol.10(4), pp.e1004235-e1004235
Publisher: Public Library Science
Number of pages: 13
Date published: 01/04/2014
Grant note: Narpes Research Foundation City of Kuopio GRANTS:15305482; MC_U106179472; G1002084; GRANTS:15326680; G0601261; GRANTS:15345979; GRANTS:15351383; MC_UU_12015/1; GRANTS:15383837; MC_UU_12015/2; GRANTS:15407037; MC_UP_A620_1017 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Swedish Heart and Lung Foundation; Swedish Heart-Lung Foundation German Diabetes Association Finska Lakaresallskapet SFO EXODIAB: Dnr 2009-1039; Dnr 521-2010-3490; Dnr 521-2007-4037; Dnr 521-2008-2974; ANDIS Dnr 825-2010-5983 / Swedish Research Council Heart and Lung Foundation; Swedish Heart-Lung Foundation MT33/09 / Torsten och Ragnar Soderbergs Stiftelser M01 RR16500 / University of Maryland General Clinical Research Center; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR)
Identifiers: 99928941102346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

A Central Role for GRB10 in Regulation of Islet Function in Man

Abstract

Files and links (1)

Metrics

Details

Usage Policy