Journal
PLOS GENETICS
Volume 10, Issue 4, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1004235
Keywords
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Categories
Funding
- Swedish Research Council [SFO EXODIAB: Dnr 2009-1039, Dnr 521-2010-3490, Dnr 521-2007-4037, Dnr 521-2008-2974, ANDIS Dnr 825-2010-5983]
- Linnaeus grant [LUDC Dnr 349-2008-6589]
- Knut & Alice Wallenberg foundation [KAW 2009.0243]
- Torsten och Ragnar Soderbergs Stiftelser [MT33/09]
- Inga Britt och Arne Lundberg's Research Foundation [359]
- Heart and Lung Foundation
- Novo Nordisk foundation
- Diabetes Research Wellness
- Sydvastra Skanes Diabetesforening
- Sigrid Juselius Foundation
- Finnish Diabetes Research Society
- Signe and Ane Gyllenberg Foundation
- Swedish Cultural Foundation in Finland
- Ollqvist Foundation
- Foundation for Life and Health in Finland
- Jakobstad Hospital
- Medical Society of Finland
- Narpes Research Foundation
- Vasa and Narpes Health centers
- Swedish Heart and Lung Foundation
- E. Lundstrom Foundation
- Region Skane County Council funds
- European Union [QLG1-CT-2001-01252]
- AstraZeneca
- NIH [R01 DK54261, R01 DK68495, U01 HL84756]
- University of Maryland General Clinical Research Center [M01 RR16500]
- Hopkins Bayview General Clinical Research Center [M01 RR02719]
- Mid-Atlantic Nutrition Obesity Research Center [P30 DK072488]
- Baltimore Diabetes Research and Training Center grant [P60 DK79637]
- Baltimore Veterans Administration Geriatric Research and Education Clinical Center
- USDA NIFA NRI Competitive Grant [2007-35205-17883]
- Ministry of Education and Culture of Finland [627]
- Academy of Finland [102318, 123885, 141069, 141226, 120386, 125876]
- Kuopio University Hospital
- Finnish Diabetes Association
- Finnish Heart Association
- Paivikki and Sakari Sohlberg Foundation
- European Commission
- City of Kuopio
- Social Insurance Institution of Finland [4/26/2010]
- Diabetes Research Foundation
- Swedish Research Council
- Swedish Heart-Lung Foundation
- Swedish Foundation for Strategic Research
- Royal Swedish Academy of Sciences
- Swedish Diabetes Foundation
- Swedish Society of Medicine
- ENGAGE (European Network for Genetic and Genomic Epidemiology) Consortium
- European Community [HEALTH-F4-2007-201413]
- Science for Life Laboratory and the Swedish Research Council for Infrastructures (RFI)
- German Research Council [DFG - SFB 1052]
- German Diabetes Association
- DHFD (Diabetes Hilfs- und Forschungsfonds Deutschland)
- Federal Ministry of Education and Research (BMBF), Germany [FKZ: 01EO1001]
- Boehringer Ingelheim Foundation
- EFSD New Horizons grant
- Development Fund of the University of Tartu, in the frame of the Centre of Transitional Genomics [SP1GVARENG]
- Estonian Government [SF0180142s08]
- European Community
- ENGAGE project [HEALTH-F4-2007-201413]
- Folkhalsan Research Foundation
- Finska Lakaresallskapet
- Liv och Halsa
- Wellcome Trust [89061/Z/09/Z, 089062/Z/09/Z, WT089062, 083270, 090367, 090532, 098381]
- Samfundet Folkhalsan
- Univeristy of Helsinki
- Ministry of Education
- Ahokas Foundation
- Emil Aaltonen Foundation
- European Science Foundation (EUROSTRESS)
- Juho Vainio Foundation
- EU Framework 7: ENGAGE Consortium [HEALTH-F4-2007-201413]
- Medical Research Council [G0601261]
- Diabetes UK [RD08/0003704]
- [LSHM-CT-2004-005272]
- MRC [G0601261, G1002084, MC_U106179472, MC_UU_12015/1, MC_UU_12015/2, MC_UP_A620_1017] Funding Source: UKRI
- Medical Research Council [G1002084, MC_UP_A620_1017, MC_U106179471, MC_UU_12015/2, G0601261, MC_UU_12015/1, MC_U106179472] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0611-10099, NF-SI-0512-10135] Funding Source: researchfish
- Novo Nordisk Fonden [NNF12OC1016467, NNF14OC0010995] Funding Source: researchfish
- Academy of Finland (AKA) [141226, 102318, 102318, 141069, 141226, 141069] Funding Source: Academy of Finland (AKA)
Ask authors/readers for more resources
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.
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