{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T12:01:29Z","timestamp":1784635289419,"version":"3.55.0"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Metabolism"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.molmet.2026.102404","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T06:25:34Z","timestamp":1781763934000},"page":"102404","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Glucokinase activity suppresses hepatic cholesterol synthesis and triglyceride accumulation: A new model for the effects of the GKRP P466L common human variant"],"prefix":"10.1016","volume":"110","author":[{"given":"Dominic","family":"Santoleri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Traynor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan P.","family":"Calhoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Gavin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Merrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7119-1615","authenticated-orcid":false,"given":"Patrick","family":"Seale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Titchenell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.molmet.2026.102404_bib1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s00018-008-8322-9","article-title":"Molecular physiology of mammalian glucokinase","volume":"66","author":"Iynedjian","year":"2009","journal-title":"Cell Mol Life Sci"},{"issue":"March","key":"10.1016\/j.molmet.2026.102404_bib2","article-title":"The central role of glucokinase in glucose homeostasis: a perspective 50 years After demonstrating the presence of the enzyme in islets of Langerhans","volume":"10","author":"Matschinsky","year":"2019","journal-title":"Front Physiol"},{"key":"10.1016\/j.molmet.2026.102404_bib3","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/j.1432-1033.1989.tb14538.x","article-title":"A protein from rat liver confers to glucokinase the property of being antagonistically regulated by fructose 6-phosphate and fructose 1-phosphate","volume":"179","author":"Van Schaftingen","year":"1989","journal-title":"Eur J Biochem"},{"key":"10.1016\/j.molmet.2026.102404_bib4","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/S0014-5793(99)00971-0","article-title":"Glucokinase regulatory protein is essential for the proper subcellular localisation of liver glucokinase","volume":"456","author":"de la Iglesia","year":"1999","journal-title":"FEBS (Fed Eur Biochem Soc) Lett"},{"issue":"14","key":"10.1016\/j.molmet.2026.102404_bib5","doi-asserted-by":"crossref","first-page":"10597","DOI":"10.1074\/jbc.275.14.10597","article-title":"The role of the regulatory protein of glucokinase in the glucose sensory mechanism of the hepatocyte","volume":"275","author":"De La Iglesia","year":"2000","journal-title":"J Biol Chem"},{"issue":"25","key":"10.1016\/j.molmet.2026.102404_bib6","doi-asserted-by":"crossref","first-page":"10171","DOI":"10.1073\/pnas.1300457110","article-title":"Molecular basis for the role of Glucokinase regulatory protein as the allosteric switch for Glucokinase","volume":"110","author":"Choi","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.molmet.2026.102404_bib7","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1042\/BJ20131363","article-title":"Analysis of the co-operative interaction between the allosterically regulated proteins GK and GKRP using tryptophan fluorescence","volume":"459","author":"Zelent","year":"2014","journal-title":"Biochem J"},{"issue":"3","key":"10.1016\/j.molmet.2026.102404_bib8","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.str.2004.02.005","article-title":"Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase","volume":"12","author":"Kamata","year":"2004","journal-title":"Structure"},{"issue":"10","key":"10.1016\/j.molmet.2026.102404_bib9","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1111\/j.1742-4658.2008.06391.x","article-title":"Catalytic activation of human glucokinase by substrate binding - residue contacts involved in the binding of D-glucose to the super-open form and conformational transitions","volume":"275","author":"Molnes","year":"2008","journal-title":"FEBS J"},{"issue":"1","key":"10.1016\/j.molmet.2026.102404_bib10","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1146\/annurev-nutr-071715-051145","article-title":"Hormonal and metabolite regulation of hepatic glucokinase","volume":"36","author":"Agius","year":"2016","journal-title":"Annu Rev Nutr"},{"key":"10.1016\/j.molmet.2026.102404_bib11","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.2337\/db07-1807","article-title":"The common P446L polymorphism in GCKR inversely modulates fasting glucose and triglyceride levels and reduces type 2 diabetes risk in the DESIR prospective general French population","volume":"57","author":"Vaxillaire","year":"2008","journal-title":"Diabetes"},{"issue":"8","key":"10.1016\/j.molmet.2026.102404_bib12","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/ng.628","article-title":"Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia","volume":"42","author":"Johansen","year":"2010","journal-title":"Nat Genet"},{"issue":"20","key":"10.1016\/j.molmet.2026.102404_bib13","doi-asserted-by":"crossref","first-page":"5570","DOI":"10.1093\/hmg\/ddu269","article-title":"Inheritance of rare functional GCKR variants and their contribution to triglyceride levels in families","volume":"23","author":"Rees","year":"2014","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.molmet.2026.102404_bib14","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.2337\/dc16-0153","article-title":"A common gene variant in glucokinase regulatory protein interacts With glucose metabolism on diabetic dyslipidemia : the combined CODAM and hoorn studies","volume":"39","author":"Simons","year":"2016","journal-title":"Diabetes Care"},{"key":"10.1016\/j.molmet.2026.102404_bib15","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.jhep.2020.04.003","article-title":"Genome-wide association study of non-alcoholic fatty liver and steatohepatitis in a histologically characterised cohort steatohepatitis in a histologically characterised cohort","volume":"73","author":"Anstee","year":"2020","journal-title":"J Hepatol"},{"issue":"11","key":"10.1016\/j.molmet.2026.102404_bib16","doi-asserted-by":"crossref","first-page":"3112","DOI":"10.2337\/db08-0516","article-title":"Common missense variant in the glucokinase regulatory protein gene Is associated With increased plasma triglyceride and C-Reactive protein but lower fasting glucose concentrations","volume":"57","author":"Orho-Melander","year":"2008","journal-title":"Diabetes"},{"issue":"7","key":"10.1016\/j.molmet.2026.102404_bib17","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1210\/jc.2010-2324","article-title":"Triglyceride response to an intensive lifestyle intervention is enhanced in carriers of the GCKR Pro446Leu polymorphism","volume":"96","author":"Pollin","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"issue":"21","key":"10.1016\/j.molmet.2026.102404_bib18","doi-asserted-by":"crossref","first-page":"4081","DOI":"10.1093\/hmg\/ddp357","article-title":"The P446L variant in GCKR associated with fasting plasma glucose and triglyceride levels exerts its effect through increased glucokinase activity in liver","volume":"18","author":"Beer","year":"2009","journal-title":"Hum Mol Genet"},{"issue":"1","key":"10.1016\/j.molmet.2026.102404_bib19","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1172\/JCI46425","article-title":"Correlation of rare coding variants in the gene encoding human glucokinase regulatory protein with phenotypic, cellular, and kinetic outcomes","volume":"122","author":"Rees","year":"2012","journal-title":"J Clin Investig"},{"key":"10.1016\/j.molmet.2026.102404_bib20","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1007\/s00125-011-2348-5","article-title":"Cellular characterisation of the GCKR P446L variant associated with type 2 diabetes risk","volume":"55","author":"Rees","year":"2012","journal-title":"Diabetologia"},{"issue":"12","key":"10.1016\/j.molmet.2026.102404_bib21","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.2337\/dc11-1200","article-title":"Effects of MK-0941, a novel glucokinase activator, on glycemic control in insulin-treated patients With type 2 diabetes","volume":"34","author":"Meininger","year":"2011","journal-title":"Diabetes Care"},{"issue":"2","key":"10.1016\/j.molmet.2026.102404_bib22","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/j.1476-5381.2012.02184.x","article-title":"Small molecule glucokinase activators disturb lipid homeostasis and induce fatty liver in rodents: a warning for therapeutic applications in humans","volume":"168","author":"De Ceuninck","year":"2013","journal-title":"Br J Pharmacol"},{"issue":"668","key":"10.1016\/j.molmet.2026.102404_bib23","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1126\/scitranslmed.abh1316","article-title":"Chronotherapy with a glucokinase activator profoundly improves metabolism in obese Zucker rats","volume":"14","author":"Kroon","year":"2022","journal-title":"Sci Transl Med"},{"issue":"April","key":"10.1016\/j.molmet.2026.102404_bib24","article-title":"The GCKR-P446L gene variant predisposes to raised blood cholesterol and lower blood glucose in the P446L mouse-a model for GCKR rs1260326","volume":"72","author":"Ford","year":"2023","journal-title":"Mol Metabol"},{"issue":"25","key":"10.1016\/j.molmet.2026.102404_bib25","doi-asserted-by":"crossref","first-page":"14511","DOI":"10.1073\/pnas.96.25.14511","article-title":"Mice mutant for glucokinase regulatory protein exhibit decreased liver glucokinase: a sequestration mechanism in metabolic regulation","volume":"96","author":"Farrelly","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"issue":"11","key":"10.1016\/j.molmet.2026.102404_bib26","doi-asserted-by":"crossref","first-page":"7826","DOI":"10.1074\/jbc.275.11.7826","article-title":"Characterization of glucokinase regulatory Protein-deficient mice \u2217","volume":"275","author":"Grimsby","year":"2000","journal-title":"J Biol Chem"},{"issue":"16","key":"10.1016\/j.molmet.2026.102404_bib27","doi-asserted-by":"crossref","first-page":"9116","DOI":"10.1073\/pnas.161284298","article-title":"A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver","volume":"98","author":"Yamashita","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"issue":"36","key":"10.1016\/j.molmet.2026.102404_bib28","doi-asserted-by":"crossref","first-page":"32746","DOI":"10.1074\/jbc.M201635200","article-title":"ChREBP rather than USF2 regulates glucose stimulation of endogenous L-pyruvate kinase expression in insulin-secreting cells","volume":"277","author":"Wang","year":"2002","journal-title":"J Biol Chem"},{"issue":"January","key":"10.1016\/j.molmet.2026.102404_bib29","article-title":"Effects of coding variants in the glucokinase regulatory protein gene on hepatic glucose and triglyceride metabolism suggest a gene regulatory function of glucokinase","volume":"166","author":"Langer","year":"2025","journal-title":"Metabolism"},{"key":"10.1016\/j.molmet.2026.102404_bib30","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0065-2571(92)90013-P","article-title":"The regulatory protein of glucokinase","volume":"32","author":"Schaftingen","year":"1992","journal-title":"Adv Enzym Regul"},{"issue":"7","key":"10.1016\/j.molmet.2026.102404_bib31","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1172\/JCI89934","article-title":"Lipogenic transcription factor ChREBP mediates fructose-induced metabolic adaptations to prevent hepatotoxicity","volume":"127","author":"Zhang","year":"2017","journal-title":"J Clin Investig"},{"issue":"3","key":"10.1016\/j.molmet.2026.102404_bib32","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S0305-0491(98)10038-X","article-title":"Phospholipid and cholesteryl ester transfer activities in plasma from 14 vertebrate species. Relation to atherogenesis susceptibility","volume":"120","author":"Guyard-Dangremont","year":"1998","journal-title":"Comp Biochem Physiol, B"},{"issue":"16","key":"10.1016\/j.molmet.2026.102404_bib33","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1021\/acs.jproteome.5b00213","article-title":"A comparison of the mouse and human lipoproteon: suitability of the mouse model for studies of human lipoproteins","volume":"14","author":"Gordon","year":"2015","journal-title":"J Proteome Res"},{"issue":"2","key":"10.1016\/j.molmet.2026.102404_bib34","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/S0021-9258(19)35415-8","article-title":"Stimulation by insulin of glucokinase gene transcription in liver of diabetic rats","volume":"263","author":"Iynedjian","year":"1988","journal-title":"J Biol Chem"},{"issue":"36","key":"10.1016\/j.molmet.2026.102404_bib35","doi-asserted-by":"crossref","first-page":"21824","DOI":"10.1016\/S0021-9258(20)88258-1","article-title":"Transcriptional induction of glucokinase gene by insulin in cultured liver cells and its repression by the glucagon-cAMP system","volume":"264","author":"Iynedjian","year":"1989","journal-title":"J Biol Chem"},{"issue":"1","key":"10.1016\/j.molmet.2026.102404_bib36","first-page":"305","article-title":"Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic Cell-specific gene Knock-outs using cre recombinase","volume":"274","author":"Postic","year":"1999"},{"issue":"2","key":"10.1016\/j.molmet.2026.102404_bib37","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1002\/hep.32759","article-title":"Rapid in vivo multiplexed editing (RIME) of the adult mouse liver","volume":"78","author":"Katsuda","year":"2023","journal-title":"Hepatology"},{"issue":"550","key":"10.1016\/j.molmet.2026.102404_bib38","first-page":"1","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"issue":"128","key":"10.1016\/j.molmet.2026.102404_bib39","article-title":"Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool","volume":"14","author":"Chen","year":"2013","journal-title":"BMC Bioinf"},{"issue":"W1","key":"10.1016\/j.molmet.2026.102404_bib40","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.molmet.2026.102404_bib41","article-title":"Gene set knowledge discovery with Enrichr","volume":"3","author":"Xie","year":"2021","journal-title":"Curr Protoc"}],"container-title":["Molecular Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2212877826000888?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2212877826000888?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T11:08:08Z","timestamp":1784632088000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2212877826000888"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":41,"alternative-id":["S2212877826000888"],"URL":"https:\/\/doi.org\/10.1016\/j.molmet.2026.102404","relation":{},"ISSN":["2212-8778"],"issn-type":[{"value":"2212-8778","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Glucokinase activity suppresses hepatic cholesterol synthesis and triglyceride accumulation: A new model for the effects of the GKRP P466L common human variant","name":"articletitle","label":"Article Title"},{"value":"Molecular Metabolism","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.molmet.2026.102404","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier GmbH.","name":"copyright","label":"Copyright"}],"article-number":"102404"}}