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

Prokopenko, Inga ; Poon, Wenny LU ; Mägi, Reedik ; Prasad, Rashmi LU ; Salehi, S Albert LU orcid ; Almgren, Peter LU ; Osmark, Peter LU ; Bouatia-Naji, Nabila ; Wierup, Nils LU and Fall, Tove LU , et al. (2014) In PLoS Genetics 10(4).
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS Genetics
volume
10
issue
4
article number
e1004235
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:24699409
  • wos:000335499600017
  • scopus:84901378366
  • pmid:24699409
ISSN
1553-7404
DOI
10.1371/journal.pgen.1004235
language
English
LU publication?
yes
id
42b2dd7a-fd3f-420c-a3d6-30e14a9d4ec1 (old id 4430862)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24699409?dopt=Abstract
date added to LUP
2016-04-01 10:53:20
date last changed
2024-11-18 20:38:13
@article{42b2dd7a-fd3f-420c-a3d6-30e14a9d4ec1,
  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       = {{Prokopenko, Inga and Poon, Wenny and Mägi, Reedik and Prasad, 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 B and F Voight, Benjamin 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}},
  issn         = {{1553-7404}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS Genetics}},
  title        = {{A Central Role for GRB10 in Regulation of Islet Function in Man.}},
  url          = {{https://lup.lub.lu.se/search/files/2209609/4882748}},
  doi          = {{10.1371/journal.pgen.1004235}},
  volume       = {{10}},
  year         = {{2014}},
}