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

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

In: PLoS Genetics, Vol. 10, No. 4, e1004235, 2014.

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Prokopenko, I, Poon, W, Mägi, R, Prasad, R, Salehi, SA, Almgren, P, Osmark, P, Bouatia-Naji, N, Wierup, N, Fall, T, Stančáková, A, Barker, A, Lagou, V, Osmond, C, Xie, W, Lahti, J, Jackson, AU, Cheng, Y-C, Liu, J, O'Connell, JR, Blomstedt, PA, Fadista, J, Alkayyali, S, Dayeh, T, Ahlqvist, E, Taneera, J, Lecoeur, C, Kumar, A, Hansson, O, Hansson, KB, F Voight, B, Kang, HM, Levy-Marchal, C, Vatin, V, Palotie, A, Syvänen, A-C, Mari, A, Weedon, MN, Loos, RJF, Ong, KK, Nilsson, P, Isomaa, B, Tuomi, T, Wareham, NJ, Stumvoll, M, Widen, E, Lakka, TA, Langenberg, C, Tönjes, A, Rauramaa, R, Kuusisto, J, Frayling, TM, Froguel, P, Walker, M, Eriksson, JG, Ling, C, Kovacs, P, Ingelsson, E, McCarthy, MI, Shuldiner, AR, Silver, KD, Laakso, M, Groop, L & Lyssenko, V 2014, 'A Central Role for GRB10 in Regulation of Islet Function in Man.', PLoS Genetics, vol. 10, no. 4, e1004235. https://doi.org/10.1371/journal.pgen.1004235

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Prokopenko I, Poon W, Mägi R, Prasad R, Salehi SA, Almgren P, Osmark P, Bouatia-Naji N, Wierup N, Fall T, Stančáková A, Barker A, Lagou V, Osmond C, Xie W, Lahti J, Jackson AU, Cheng Y-C, Liu J, O'Connell JR, Blomstedt PA, Fadista J, Alkayyali S, Dayeh T, Ahlqvist E, Taneera J, Lecoeur C, Kumar A, Hansson O, Hansson KB, F Voight B, Kang HM, Levy-Marchal C, Vatin V, Palotie A, Syvänen A-C, Mari A, Weedon MN, Loos RJF, Ong KK, Nilsson P, Isomaa B, Tuomi T, Wareham NJ, Stumvoll M, Widen E, Lakka TA, Langenberg C, Tönjes A, Rauramaa R, Kuusisto J, Frayling TM, Froguel P, Walker M, Eriksson JG, Ling C, Kovacs P, Ingelsson E, McCarthy MI, Shuldiner AR, Silver KD, Laakso M, Groop L, Lyssenko V. 2014. A Central Role for GRB10 in Regulation of Islet Function in Man. PLoS Genetics. 10(4). https://doi.org/10.1371/journal.pgen.1004235

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Prokopenko, Inga ; Poon, Wenny ; Mägi, Reedik ; Prasad, Rashmi ; Salehi, S Albert ; Almgren, Peter ; Osmark, Peter ; Bouatia-Naji, Nabila ; Wierup, Nils ; Fall, Tove ; Stančáková, Alena ; Barker, Adam ; Lagou, Vasiliki ; Osmond, Clive ; Xie, Weijia ; Lahti, Jari ; Jackson, Anne U ; Cheng, Yu-Ching ; Liu, Jie ; O'Connell, Jeffrey R ; Blomstedt, Paul A ; Fadista, Joao ; Alkayyali, Sami ; Dayeh, Tasnim ; Ahlqvist, Emma ; Taneera, Jalal ; Lecoeur, Cecile ; Kumar, Ashish ; Hansson, Ola ; Hansson, Karin B ; F Voight, Benjamin ; Kang, Hyun Min ; Levy-Marchal, Claire ; Vatin, Vincent ; Palotie, Aarno ; Syvänen, Ann-Christine ; Mari, Andrea ; Weedon, Michael N ; Loos, Ruth J F ; Ong, Ken K ; Nilsson, Peter ; Isomaa, Bo ; Tuomi, Tiinamaija ; Wareham, Nicholas J ; Stumvoll, Michael ; Widen, Elisabeth ; Lakka, Timo A ; Langenberg, Claudia ; Tönjes, Anke ; Rauramaa, Rainer ; Kuusisto, Johanna ; Frayling, Timothy M ; Froguel, Philippe ; Walker, Mark ; Eriksson, Johan G ; Ling, Charlotte ; Kovacs, Peter ; Ingelsson, Erik ; McCarthy, Mark I ; Shuldiner, Alan R ; Silver, Kristi D ; Laakso, Markku ; Groop, Leif ; Lyssenko, Valeriya. / A Central Role for GRB10 in Regulation of Islet Function in Man. In: PLoS Genetics. 2014 ; Vol. 10, No. 4.

RIS

TY - JOUR

T1 - A Central Role for GRB10 in Regulation of Islet Function in Man.

AU - Prokopenko, Inga

AU - Poon, Wenny

AU - Mägi, Reedik

AU - Prasad, Rashmi

AU - Salehi, S Albert

AU - Almgren, Peter

AU - Osmark, Peter

AU - Bouatia-Naji, Nabila

AU - Wierup, Nils

AU - Fall, Tove

AU - Stančáková, Alena

AU - Barker, Adam

AU - Lagou, Vasiliki

AU - Osmond, Clive

AU - Xie, Weijia

AU - Lahti, Jari

AU - Jackson, Anne U

AU - Cheng, Yu-Ching

AU - Liu, Jie

AU - O'Connell, Jeffrey R

AU - Blomstedt, Paul A

AU - Fadista, Joao

AU - Alkayyali, Sami

AU - Dayeh, Tasnim

AU - Ahlqvist, Emma

AU - Taneera, Jalal

AU - Lecoeur, Cecile

AU - Kumar, Ashish

AU - Hansson, Ola

AU - Hansson, Karin B

AU - F Voight, Benjamin

AU - Kang, Hyun Min

AU - Levy-Marchal, Claire

AU - Vatin, Vincent

AU - Palotie, Aarno

AU - Syvänen, Ann-Christine

AU - Mari, Andrea

AU - Weedon, Michael N

AU - Loos, Ruth J F

AU - Ong, Ken K

AU - Nilsson, Peter

AU - Isomaa, Bo

AU - Tuomi, Tiinamaija

AU - Wareham, Nicholas J

AU - Stumvoll, Michael

AU - Widen, Elisabeth

AU - Lakka, Timo A

AU - Langenberg, Claudia

AU - Tönjes, Anke

AU - Rauramaa, Rainer

AU - Kuusisto, Johanna

AU - Frayling, Timothy M

AU - Froguel, Philippe

AU - Walker, Mark

AU - Eriksson, Johan G

AU - Ling, Charlotte

AU - Kovacs, Peter

AU - Ingelsson, Erik

AU - McCarthy, Mark I

AU - Shuldiner, Alan R

AU - Silver, Kristi D

AU - Laakso, Markku

AU - Groop, Leif

AU - Lyssenko, Valeriya

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pgen.1004235

DO - 10.1371/journal.pgen.1004235

M3 - Article

VL - 10

JO - PLoS Genetics

T2 - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7404

IS - 4

M1 - e1004235

ER -