{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Prokopenko I"],"funding":["NIDDK NIH HHS","NCRR NIH HHS","Medical Research Council","NHLBI NIH HHS","National Institute for Health Research (NIHR)","Wellcome Trust","Novo Nordisk Fonden"],"pagination":["e1004235"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3974640"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(4)"],"pubmed_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."],"journal":["PLoS genetics"],"pubmed_title":["A central role for GRB10 in regulation of islet function in man."],"pmcid":["PMC3974640"],"funding_grant_id":["089062","U01 HL084756","P60 DK079637","P60 DK79637","M01 RR002719","090532","MC_UU_12015/1","R01 DK54261","89061/Z/09/Z","M01 RR016500","WT089062","089062/Z/09/Z","P30 DK072488","NNF14OC0010995","083270","NNF12OC1016467","P30 DK079637","M01 RR16500","NF-SI-0611-10099","098381","U01 HL84756","G0601261","R01 DK68495","R01 DK054261","MC_UP_A620_1017","G1002084","MC_U106179472","MC_UU_12015/2","MC_U106179471","090367","R01 DK068495","NF-SI-0512-10135","M01 RR02719"],"pubmed_authors":["McCarthy MI","Barker A","Lyssenko V","Fadista J","Prasad B R","Palotie A","Stumvoll M","Ling C","Stancakova A","Dayeh T","Prokopenko I","Tonjes A","Almgren P","Syvanen AC","Hansson K","Frayling TM","Lahti J","O'Connell JR","Salehi SA","Lecoeur C","Kang HM","Xie W","Walker M","Groop L","Magi R","Loos RJ","Poon W","Hansson O","Shuldiner AR","Taneera J","Eriksson JG","Lagou V","Ong KK","Osmark P","Mari A","Rauramaa R","Laakso M","Voight BF","Tuomi T","Bouatia-Naji N","Jackson AU","Liu J","Osmond C","Ingelsson E","Isomaa B","Vatin V","Wareham NJ","Widen E","Cheng YC","Kovacs P","Wierup N","Silver KD","Blomstedt PA","Langenberg C","Ahlqvist E","Kuusisto J","Levy-Marchal C","Fall T","Weedon MN","Froguel P","Nilsson P","Kumar A","Lakka TA","Alkayyali S"],"additional_accession":[]},"is_claimable":false,"name":"A central role for GRB10 in regulation of islet function in man.","description":"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.","dates":{"release":"2014-01-01T00:00:00Z","publication":"2014 Apr","modification":"2024-11-07T11:12:07.638Z","creation":"2019-03-27T01:24:25Z"},"accession":"S-EPMC3974640","cross_references":{"pubmed":["24699409"],"doi":["10.1371/journal.pgen.1004235"]}}