%0 Journal Article
%T A Central Role for GRB10 in Regulation of Islet Function in Man
%A Aarno Palotie
%A Adam Barker
%A Alan R. Shuldiner
%A Alena Stan£¿¨¢kov¨¢
%A Andrea Mari
%A Anke T£¿njes
%A Ann-Christine Syv£¿nen
%A Anne U. Jackson
%A Ashish Kumar
%A Benjamin F. Voight
%A Bo Isomaa
%A Cecile Lecoeur
%A Charlotte Ling
%A Claire Levy-Marchal
%A Claudia Langenberg
%A Clive Osmond
%A Elisabeth Widen
%A Emma Ahlqvist
%A Erik Ingelsson
%A Hyun Min Kang
%A Inga Prokopenko
%A Jalal Taneera
%A Jari Lahti
%A Jeffrey R. O'Connell
%A Jie Liu
%A Joao Fadista
%A Johan G. Eriksson
%A Johanna Kuusisto
%A Karin Hansson
%A Ken K. Ong
%A Kristi D. Silver
%A Leif Groop
%A Mark I. McCarthy
%A Mark Walker
%A Markku Laakso
%A Michael N. Weedon
%A Michael Stumvoll
%A Nabila Bouatia-Naji
%A Nicholas J. Wareham
%A Nils Wierup
%A Ola Hansson
%A Paul A. Blomstedt
%A Peter Almgren
%A Peter Kovacs
%A Peter Nilsson
%A Peter Osmark
%A Philippe Froguel
%A Rainer Rauramaa
%A Rashmi Prasad B
%A Reedik M£¿gi
%A Ruth J. F. Loos
%A S. Albert Salehi
%A Sami Alkayyali
%A Tasnim Dayeh
%A Tiinamaija Tuomi
%A Timo A. Lakka
%A Timothy M. Frayling
%A Tove Fall
%A Valeriya Lyssenko
%A Vasiliki Lagou
%A Vincent Vatin
%A Weijia Xie
%A Wenny Poon
%A Yu-Ching Cheng
%J -
%D 2014
%R 10.1371/journal.pgen.1004235
%X 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
%K Insulin
%K DNA methylation
%K Insulin secretion
%K Glucagon
%K Genome-wide association studies
%K Meta-analysis
%K Methylation
%K Molecular genetics
%U https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004235