{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:46:10Z","timestamp":1788522370425,"version":"build-2803163510"},"reference-count":104,"publisher":"Korean Diabetes Association","issue":"1","license":[{"start":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T00:00:00Z","timestamp":1643241600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["e-dmj.org"],"crossmark-restriction":true},"short-container-title":["Diabetes Metab J"],"published-print":{"date-parts":[[2022,1,31]]},"abstract":"<jats:p>The main pathogenic mechanism of diabetes consists of an increase in insulin resistance and a decrease in insulin secretion from pancreatic \u03b2-cells. The number of diabetic patients has been increasing dramatically worldwide, especially in Asian people whose capacity for insulin secretion is inherently lower than that of other ethnic populations. Causally, changes of environmental factors in addition to intrinsic genetic factors have been considered to have an influence on the increased prevalence of diabetes. Particular focus has been placed on \u201cgene-environment interactions\u201d in the development of a reduced pancreatic \u03b2-cell mass, as well as type 1 and type 2 diabetes mellitus. Changes in the intrauterine environment, such as intrauterine growth restriction, contribute to alterations of gene expression in pancreatic \u03b2-cells, ultimately resulting in the development of pancreatic \u03b2-cell failure and diabetes. As a molecular mechanism underlying the effect of the intrauterine environment, epigenetic modifications have been widely investigated. The association of diabetes susceptibility genes or dietary habits with gene-environment interactions has been reported. In this review, we provide an overview of the role of gene-environment interactions in pancreatic \u03b2-cell failure as revealed by previous reports and data from experiments.<\/jats:p>","DOI":"10.4093\/dmj.2021.0045","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T02:25:04Z","timestamp":1643336704000},"page":"38-48","update-policy":"https:\/\/doi.org\/10.4093\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Regulation of Pancreatic \u03b2-Cell Mass by Gene-Environment Interaction"],"prefix":"10.4093","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6661-9402","authenticated-orcid":true,"given":"Shun-ichiro","family":"Asahara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2433-5799","authenticated-orcid":true,"given":"Yoshiaki","family":"Kido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2567","reference":[{"key":"ref1","volume-title":"","year":"2019"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/s2213-8587(15)00389-7"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-015-0602-9"},{"key":"ref4","first-page":"67","volume-title":"Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in East Asians","author":"Cho","year":"2011"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1038\/ng1774"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.01695-07"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023238"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0970"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000324"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2012.141"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.8.1662"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.37.9.1163"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1992.262.6.r1025"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(95)90123-x"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.12.3274"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.23.9.1353"},{"key":"ref17","first-page":"2170","volume-title":"Beta-cell function is a major contributor to oral glucose tolerance in high-risk relatives of four ethnic groups in the U.S","author":"Jensen","year":"2002"},{"key":"ref18","first-page":"144","volume-title":"The relationship between dysglycemia and atherosclerosis in South Asian, Chinese, and European individuals in Canada: a randomly sampled cross-sectional study","author":"Gerstein","year":"2003"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13242"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12098"},{"key":"ref21","first-page":"111","volume-title":"\u03b2-Cell mass and turnover in humans: effects of obesity and aging","author":"Saisho","year":"2013"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-1373"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13447"},{"key":"ref24","first-page":"32","volume-title":"Pancreatic beta-cell mass in European subjects with type 2 diabetes","author":"Rahier","year":"2008"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(86)91340-1"},{"key":"ref26","first-page":"249","volume-title":"Leptin and insulin in young adulthood areassociated with weight in infancy","author":"Simeoni","year":"2020"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1017\/jns.2014.69"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010818-021304"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19092584"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2018.02.006"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1016\/s0303-7207(01)00721-3"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1097\/hjh.0b013e328012135b"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.05.005"},{"key":"ref34","first-page":"411","volume-title":"Lifespan: catch-up growth and obesity in male mice","author":"Ozanne","year":"2004"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1542\/peds.109.2.194"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1159\/000509932"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1186\/s12937-018-0397-z"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-018-4694-z"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.1007\/s13340-013-0127-x"},{"key":"ref40","first-page":"325","volume-title":"Effect of intrauterine undernutrition during late gestation on pancreatic beta cell mass","author":"Inoue","year":"2009"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.3945\/jn.111.144717"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1770235"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-1669-7"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.1172\/jci32661"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.1038\/nature09491"},{"key":"ref46","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1991.260.6.l386"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-019-0079-0"},{"key":"ref48","first-page":"602477","volume-title":"Genetics and epigenetics: new insight on gestational diabetes mellitus","author":"Dalfra","year":"2020"},{"key":"ref49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0177468"},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2014.01.045"},{"key":"ref51","doi-asserted-by":"publisher","DOI":"10.3390\/biom10101359"},{"key":"ref52","doi-asserted-by":"publisher","DOI":"10.1172\/jci33655"},{"key":"ref53","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1019007108"},{"key":"ref54","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008887"},{"key":"ref55","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0216665"},{"key":"ref56","doi-asserted-by":"publisher","DOI":"10.3390\/nu7021202"},{"key":"ref57","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m800128200"},{"key":"ref58","doi-asserted-by":"publisher","DOI":"10.2337\/db11-1834"},{"key":"ref59","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.03.026"},{"key":"ref60","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(13)60591-7"},{"key":"ref61","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.2864"},{"key":"ref62","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2015-000161"},{"key":"ref63","doi-asserted-by":"publisher","DOI":"10.2174\/1573399811666150421114957"},{"key":"ref64","first-page":"857","volume-title":"Incidence and trends of childhood type 1 diabetes worldwide 1990-1999","year":"2006"},{"key":"ref65","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(09)60568-7"},{"key":"ref66","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-011-0223-x"},{"key":"ref67","doi-asserted-by":"publisher","DOI":"10.2337\/dc19-0986"},{"key":"ref68","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2016.08.005"},{"key":"ref69","first-page":"1377","volume-title":"Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants","year":"2016"},{"key":"ref70","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0242105"},{"key":"ref71","first-page":"2627","volume-title":"Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128\u00b79 million children, adolescents, and adults","year":"2017"},{"key":"ref72","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-018-3224-9"},{"key":"ref73","doi-asserted-by":"publisher","DOI":"10.1210\/er.2017-00191"},{"key":"ref74","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-018-4763-3"},{"key":"ref75","volume-title":""},{"key":"ref76","doi-asserted-by":"publisher","DOI":"10.1007\/s00508-018-1434-9"},{"key":"ref77","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-2331"},{"key":"ref78","doi-asserted-by":"publisher","DOI":"10.1172\/jci92035"},{"key":"ref79","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(16)30507-4"},{"key":"ref80","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03168-4"},{"key":"ref81","doi-asserted-by":"publisher","DOI":"10.1111\/pedi.12115"},{"key":"ref82","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.1294"},{"key":"ref83","doi-asserted-by":"publisher","DOI":"10.1001\/jama.290.13.1721"},{"key":"ref84","first-page":"522","volume-title":"Early infant diet and islet autoimmunity in the TEDDY study","author":"Uusitalo","year":"2018"},{"key":"ref85","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.30"},{"key":"ref86","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2762-3"},{"key":"ref87","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13387"},{"key":"ref88","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4289"},{"key":"ref89","doi-asserted-by":"publisher","DOI":"10.1038\/ng.207"},{"key":"ref90","doi-asserted-by":"publisher","DOI":"10.1038\/ng.208"},{"key":"ref91","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1335-6"},{"key":"ref92","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0246"},{"key":"ref93","first-page":"1445","volume-title":"Genetic variation in KCNQ1 associates with fasting glucose and betacell function: a study of 3,734 subjects comprising three ethnicities living in Singapore","author":"Tan","year":"2009"},{"key":"ref94","doi-asserted-by":"publisher","DOI":"10.2337\/db11-1516"},{"key":"ref95","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1422104112"},{"key":"ref96","first-page":"115","volume-title":"Ablation of C\/EBPbeta alleviates ER stress and pancreatic beta cell failure through the GRP78 chaperone in mice","author":"Matsuda","year":"2010"},{"key":"ref97","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0130757"},{"key":"ref98","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2008.06818.x"},{"key":"ref99","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.22.19.6681-6688.2002"},{"key":"ref100","first-page":"103","volume-title":"The GCN2 eIF2alpha kinase regulates fatty-acid homeostasis in the liver during deprivation of an essential amino acid","author":"Guo","year":"2007"},{"key":"ref101","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2009.17"},{"key":"ref102","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.128820"},{"key":"ref103","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.02.024"},{"key":"ref104","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07201-1"}],"container-title":["Diabetes &amp; Metabolism Journal"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/e-dmj.org\/upload\/pdf\/dmj-2021-0045.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-dmj.org\/journal\/view.php?doi=10.4093\/dmj.2021.0045","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-dmj.org\/upload\/pdf\/dmj-2021-0045.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T21:44:50Z","timestamp":1645739090000},"score":1,"resource":{"primary":{"URL":"http:\/\/e-dmj.org\/journal\/view.php?doi=10.4093\/dmj.2021.0045"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,31]]},"references-count":104,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"URL":"https:\/\/doi.org\/10.4093\/dmj.2021.0045","relation":{},"ISSN":["2233-6079","2233-6087"],"issn-type":[{"value":"2233-6079","type":"print"},{"value":"2233-6087","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,31]]},"assertion":[{"value":"2021-03-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-27","order":2,"name":"published","label":"Published online","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-31","order":3,"name":"published","label":"Print publication","group":{"name":"publication_history","label":"Publication History"}}]}}