作者
Inga Prokopenko, Wenny Poon, Reedik Maegi, Rashmi Prasad B, S Albert Salehi, Peter Almgren, Peter Osmark, Nabila Bouatia-Naji, Nils Wierup, Tove Fall, Alena Stančáková, 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 Syvänen, Andrea Mari, Michael N Weedon, Ruth JF Loos, Ken K Ong, Peter Nilsson, Bo Isomaa, Tiinamaija Tuomi, Nicholas J Wareham, Michael Stumvoll, Elisabeth Widen, Timo A Lakka, Claudia Langenberg, Anke Tönjes, 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
发表日期
2014/4/3
期刊
PLoS genetics
卷号
10
期号
4
页码范围
e1004235
出版商
Public Library of Science
简介
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.
学术搜索中的文章
I Prokopenko, W Poon, R Maegi, R Prasad B… - PLoS genetics, 2014