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

Research output: Contribution to journalArticle


title = "A Central Role for GRB10 in Regulation of Islet Function in Man.",
abstract = "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.",
author = "Inga Prokopenko and Wenny Poon and Reedik M{\"a}gi and Rashmi Prasad and Salehi, {S Albert} and Peter Almgren and Peter Osmark and Nabila Bouatia-Naji and Nils Wierup and Tove Fall and Alena Stanč{\'a}kov{\'a} and Adam Barker and Vasiliki Lagou and Clive Osmond and Weijia Xie and Jari Lahti and Jackson, {Anne U} and Yu-Ching Cheng and Jie Liu and O'Connell, {Jeffrey R} and Blomstedt, {Paul A} and Joao Fadista and Sami Alkayyali and Tasnim Dayeh and Emma Ahlqvist and Jalal Taneera and Cecile Lecoeur and Ashish Kumar and Ola Hansson and Hansson, {Karin B} and {F Voight}, Benjamin and Kang, {Hyun Min} and Claire Levy-Marchal and Vincent Vatin and Aarno Palotie and Ann-Christine Syv{\"a}nen and Andrea Mari and Weedon, {Michael N} and Loos, {Ruth J F} and Ong, {Ken K} and Peter Nilsson and Bo Isomaa and Tiinamaija Tuomi and Wareham, {Nicholas J} and Michael Stumvoll and Elisabeth Widen and Lakka, {Timo A} and Claudia Langenberg and Anke T{\"o}njes and Rainer Rauramaa and Johanna Kuusisto and Frayling, {Timothy M} and Philippe Froguel and Mark Walker and Eriksson, {Johan G} and Charlotte Ling and Peter Kovacs and Erik Ingelsson and McCarthy, {Mark I} and Shuldiner, {Alan R} and Silver, {Kristi D} and Markku Laakso and Leif Groop and Valeriya Lyssenko",
year = "2014",
doi = "10.1371/journal.pgen.1004235",
language = "English",
volume = "10",
journal = "PLoS Genetics",
issn = "1553-7404",
publisher = "Public Library of Science",
number = "4",