A central role for GRB10 in regulation of islet function in man

Prokopenko, Inga and Poon, Wenny and Mägi, Reedik and Prasad B, Rashmi and Salehi, S. Albert and Almgren, Peter and Osmark, Peter and Bouatia-Naji, Nabila and Wierup, Nils and Fall, Tove and Stančáková, Alena and Barker, Adam and Lagou, Vasiliki and Osmond, Clive and Xie, Weijia and Lahti, Jari and Jackson, Anne U. and Cheng, Yu-Ching and Liu, Jie and O'Connell, Jeffrey R. and Blomstedt, Paul A. and Fadista, Joao and Alkayyali, Sami and Dayeh, Tasnim and Ahlqvist, Emma and Taneera, Jalal and Lecoeur, Cecile and Kumar, Ashish and Hansson, Ola and Hansson, Karin and Voight, Benjamin F. and Kang, Hyun Min and Levy-Marchal, Claire and Vatin, Vincent and Palotie, Aarno and Syvänen, Ann-Christine and Mari, Andrea and Weedon, Michael N. and Loos, Ruth J. F. and Ong, Ken K. and Nilsson, Peter and Isomaa, Bo and Tuomi, Tiinamaija and Wareham, Nicholas J. and Stumvoll, Michael and Widen, Elisabeth and Lakka, Timo A. and Langenberg, Claudia and Tönjes, Anke and Rauramaa, Rainer and Kuusisto, Johanna and Frayling, Timothy M. and Froguel, Philippe and Walker, Mark and Eriksson, Johan G. and Ling, Charlotte and Kovacs, Peter and Ingelsson, Erik and McCarthy, Mark I. and Shuldiner, Alan R. and Silver, Kristi D. and Laakso, Markku and Groop, Leif and Lyssenko, Valeriya. (2014) A central role for GRB10 in regulation of islet function in man. PLoS genetics, Vol. 10, H. 4 , e1004235.

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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.

Faculties and Departments:	09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) 09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Exposome Science (Probst-Hensch) 03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Exposome Science (Probst-Hensch)
UniBasel Contributors:	Kumar, Ashish
Item Type:	Article, refereed
Article Subtype:	Research Article
Publisher:	Public Library of Science
ISSN:	1553-7390
Note:	Publication type according to Uni Basel Research Database: Journal article
Language:	English
Related URLs:	Document
Identification Number:	pmid: 24699409
edoc DOI:	10.5451/unibas-ep33874
Last Modified:	31 Dec 2015 10:56
Deposited On:	15 Aug 2014 07:16

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