{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T20:59:18Z","timestamp":1764277158587,"version":"3.37.3"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Gastrointestinal-mediated glucose disposal (GIGD) during oral glucose tolerance test (OGTT) reflects the percentage of glucose disposal caused by mechanisms elicited by the oral route of glucose administration. GIGD is reduced in patients with type 2 diabetes (T2D) due to a reduced incretin effect and possibly also due to inappropriate suppression of glucagon after oral glucose. We investigated the effect of glucagon receptor antagonism on GIGD, the incretin effect and glucose excursions in patients with T2D and controls without diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>A double-blind, randomised, placebo-controlled crossover study was conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ten patients with T2D and 10 gender-, age- and BMI-matched controls underwent two 50 g OGTTs and 2 isoglycaemic i.v. glucose infusions, succeeding (~10 h) single-dose administration of 100 mg of the glucagon receptor antagonist LY2409021 or placebo, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to placebo, LY2409021 reduced fasting plasma glucose in patients with T2D and controls. Plasma glucose excursions after oral glucose assessed by baseline-subtracted area under the curve were increased by LY2409021 compared to placebo in both groups, but no effect of LY2409021 on GIGD or the incretin effect was observed. LY2409021 increased fasting glucagon concentrations three-fold compared to placebo concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Glucagon receptor antagonism with LY2409021 had no effect on the impaired GIGD or the impaired incretin effect in patients with T2D and did also not affect these parameters in the controls. Surprisingly, we observed reduced oral glucose tolerance with LY2409021 which may be specific for this glucagon receptor antagonist.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-22-0291","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T18:30:26Z","timestamp":1660761026000},"page":"507-518","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":4,"title":["The glucagon receptor antagonist LY2409021 does not affect gastrointestinal-mediated glucose disposal or the incretin effect in individuals with and without type 2 diabetes"],"prefix":"10.1093","volume":"187","author":[{"given":"Sofie","family":"H\u00e6dersdal","sequence":"first","affiliation":[{"name":"Clinical Research, Copenhagen University Hospital \u2013 Steno Diabetes Center Copenhagen , Herlev, Denmark"},{"name":"Center for Clinical Metabolic Research, Copenhagen University Hospital \u2013 Herlev and Gentofte , Hellerup, Denmark"},{"name":"Danish Diabetes Academy, Odense University Hospital , Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asger","family":"Lund","sequence":"additional","affiliation":[{"name":"Clinical Research, Copenhagen University Hospital \u2013 Steno Diabetes Center Copenhagen , Herlev, Denmark"},{"name":"Center for Clinical Metabolic Research, Copenhagen University Hospital \u2013 Herlev and Gentofte , Hellerup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Nielsen-Hannerup","sequence":"additional","affiliation":[{"name":"Clinical Research, Copenhagen University Hospital \u2013 Steno Diabetes Center Copenhagen , Herlev, Denmark"},{"name":"Center for Clinical Metabolic Research, Copenhagen University Hospital \u2013 Herlev and Gentofte , Hellerup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Maagensen","sequence":"additional","affiliation":[{"name":"Clinical Research, Copenhagen University Hospital \u2013 Steno Diabetes Center Copenhagen , Herlev, Denmark"},{"name":"Center for Clinical Metabolic Research, Copenhagen University Hospital \u2013 Herlev and Gentofte , Hellerup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie L","family":"Forman","sequence":"additional","affiliation":[{"name":"Department of Public Health, Section of Biostatistics, University of Copenhagen , Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens J","family":"Holst","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark"},{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2495-5034","authenticated-orcid":false,"given":"Filip K","family":"Knop","sequence":"additional","affiliation":[{"name":"Clinical Research, Copenhagen University Hospital \u2013 Steno Diabetes Center Copenhagen , Herlev, Denmark"},{"name":"Center for Clinical Metabolic Research, Copenhagen University Hospital \u2013 Herlev and Gentofte , Hellerup, Denmark"},{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0456-6787","authenticated-orcid":false,"given":"Tina","family":"Vilsb\u00f8ll","sequence":"additional","affiliation":[{"name":"Clinical Research, Copenhagen University Hospital \u2013 Steno Diabetes Center Copenhagen , Herlev, Denmark"},{"name":"Center for Clinical Metabolic Research, Copenhagen University Hospital \u2013 Herlev and Gentofte , Hellerup, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"2023010809171793800_bib1","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1210\/jcem-64-1-106","article-title":"Documentation of hyperglucagonemia throughout the day in nonobese and obese patients with noninsulin-dependent diabetes mellitus","volume":"64","author":"Reaven","year":"1987","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"2023010809171793800_bib2","doi-asserted-by":"crossref","first-page":"274","DOI":"10.2337\/diab.36.3.274","article-title":"Role of hyperglucagonemia in maintenance of increased rates of hepatic glucose output in type II diabetics","volume":"36","author":"Baron","year":"1987","journal-title":"Diabetes"},{"key":"2023010809171793800_bib3","first-page":"E283","article-title":"Impact of lack of suppression of glucagon on glucose tolerance in humans","volume":"277","author":"Shah","year":"1999","journal-title":"American Journal of Physiology"},{"key":"2023010809171793800_bib4","first-page":"4053","article-title":"Lack of suppression of glucagon contributes to postprandial hyperglycemia in subjects with type 2 diabetees mellitus","volume":"85","author":"Shah","year":"2000","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"2023010809171793800_bib5","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1210\/er.2018-00251","article-title":"The liver-\u03b1-cell axis and type 2 diabetes","volume":"40","author":"Wewer Albrechtsen","year":"2019","journal-title":"Endocrine Reviews"},{"key":"2023010809171793800_bib6","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1007\/s00125-006-0566-z","article-title":"Inappropriate suppression of glucagon during OGTT but not during isoglycaemic i.v. glucose infusion contributes to the reduced incretin effect in type 2 diabetes mellitus","volume":"50","author":"Knop","year":"2007","journal-title":"Diabetologia"},{"key":"2023010809171793800_bib7","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1007\/s00125-014-3264-2","article-title":"Glucagon responses to increasing oral loads of glucose and corresponding isoglycaemic intravenous glucose infusions in patients with type 2 diabetes and healthy individuals","volume":"57","author":"Bagger","year":"2014","journal-title":"Diabetologia"},{"key":"2023010809171793800_bib8","doi-asserted-by":"crossref","first-page":"4377","DOI":"10.1210\/jc.2016-1948","article-title":"Higher endogenous glucose production during OGTT vs isoglycemic intravenous glucose infusion","volume":"101","author":"Lund","year":"2016","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"2023010809171793800_bib9","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.2337\/db07-0100","article-title":"Reduced incretin effect in type 2 diabetes: cause or consequence of the diabetic state?","volume":"56","author":"Knop","year":"2007","journal-title":"Diabetes"},{"key":"2023010809171793800_bib10","doi-asserted-by":"crossref","first-page":"R267","DOI":"10.1530\/EJE-18-0197","article-title":"EJE PRIZE 2018: a gut feeling about glucagon","volume":"178","author":"Knop","year":"2018","journal-title":"European Journal of Endocrinology"},{"key":"2023010809171793800_bib11","doi-asserted-by":"crossref","first-page":"585","DOI":"10.2337\/db15-1541","article-title":"Evidence of extrapancreatic glucagon secretion in man","volume":"65","author":"Lund","year":"2016","journal-title":"Diabetes"},{"key":"2023010809171793800_bib12","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.diabres.2018.06.013","article-title":"Extrapancreatic glucagon: present status","volume":"147","author":"Lund","year":"2019","journal-title":"Diabetes Research and Clinical Practice"},{"key":"2023010809171793800_bib13","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/BF02427280","article-title":"Reduced incretin effect in type 2 (non-insulin-dependent) diabetes","volume":"29","author":"Nauck","year":"1986","journal-title":"Diabetologia"},{"key":"2023010809171793800_bib14","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1007\/s00125-002-0878-6","article-title":"Defective amplification of the late phase insulin response to glucose by gip in obese type ii diabetic patients","volume":"45","author":"Vilsb\u00f8ll","year":"2002","journal-title":"Diabetologia"},{"key":"2023010809171793800_bib15","first-page":"E832","article-title":"Inappropriate glucagon response after oral compared with isoglycemic intravenous glucose administration in patients with type 1 diabetes","volume":"298","author":"Hare","year":"2010","journal-title":"American Journal of Physiology: Endocrinology and Metabolism"},{"key":"2023010809171793800_bib16","doi-asserted-by":"crossref","first-page":"3309","DOI":"10.1210\/jc.2010-0119","article-title":"Reduced glucose tolerance and insulin resistance induced by steroid treatment, relative physical inactivity, and high-calorie diet impairs the incretin effect in healthy subjects","volume":"95","author":"Hansen","year":"2010","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"2023010809171793800_bib17","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1210\/jcem-63-2-492","article-title":"Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses","volume":"63","author":"Nauck","year":"1986","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"2023010809171793800_bib18","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1530\/EJE-21-0865","article-title":"The glucagon receptor antagonist LY2409021 has no effect on postprandial glucose in type 2 diabetes","volume":"186","author":"H\u00e6dersdal","year":"2022","journal-title":"European Journal of Endocrinology"},{"volume-title":"Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycaemia. Report of a WHO\/IDF Consultation","year":"2006","author":"World Health Organization","key":"2023010809171793800_bib19"},{"key":"2023010809171793800_bib20","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1111\/dom.12446","article-title":"Short-term administration of the glucagon receptor antagonist LY2409021 lowers blood glucose in healthy people and in those with type 2 diabetes","volume":"17","author":"Kelly","year":"2015","journal-title":"Diabetes, Obesity and Metabolism"},{"key":"2023010809171793800_bib21","first-page":"dc151643","article-title":"A randomized, double-blind, placebo-controlled phase 2 study of the glucagon receptor antagonist LY2409021 in patients with type 2 diabetes","volume":"39","author":"Kazda","year":"2015","journal-title":"Diabetes Care"},{"key":"2023010809171793800_bib22","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.2337\/dc15-1643","article-title":"Evaluation of efficacy and safety of the glucagon receptor antagonist LY2409021 in patients with type 2 diabetes: 12- and 24-week phase 2 studies","author":"Kazda","year":"2016","journal-title":"Diabetes Care"},{"key":"2023010809171793800_bib23","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1530\/EJE-13-0941","article-title":"Specificity and sensitivity of commercially available assays for glucagon and oxyntomodulin measurement in humans","volume":"170","author":"Bak","year":"2014","journal-title":"European Journal of Endocrinology"},{"key":"2023010809171793800_bib24","doi-asserted-by":"crossref","first-page":"535","DOI":"10.2337\/diab.43.4.535","article-title":"Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide I in humans","volume":"43","author":"\u00d8rskov","year":"1994","journal-title":"Diabetes"},{"key":"2023010809171793800_bib25","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1210\/jc.2011-0266","article-title":"Incretin hormone and insulin responses to oral versus intravenous lipid administration in humans","volume":"96","author":"Lindgren","year":"2011","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"2023010809171793800_bib26","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/cen.12167","article-title":"The incretin effect in Korean subjects with normal glucose tolerance or type 2 diabetes","volume":"80","author":"Oh","year":"2014","journal-title":"Clinical Endocrinology"},{"key":"2023010809171793800_bib27","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0169-2607(96)01755-5","article-title":"ISEC: a program to calculate insulin secretion","volume":"50","author":"Hovorka","year":"1996","journal-title":"Computer Methods and Programs in Biomedicine"},{"key":"2023010809171793800_bib28","doi-asserted-by":"crossref","first-page":"580","DOI":"10.2337\/diabetes.49.4.580","article-title":"Validation of methods for measurment of Ins secretion in human in vivo","volume":"49","author":"Kjems","year":"2000","journal-title":"Diabetes"},{"key":"2023010809171793800_bib29","doi-asserted-by":"crossref","DOI":"10.1201\/b17537","volume-title":"Design and Analysis of Cross-Over Trials","author":"Jones","year":"2014","edition":"3rd ed."},{"key":"2023010809171793800_bib30","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate \u2013 a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"Journal of the Royal Statistical Society: Series B"},{"key":"2023010809171793800_bib31","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1177\/1932296815576957","article-title":"How to assess the quality of glucose clamps? Evaluation of clamps performed with ClampArt, a novel automated clamp device","volume":"9","author":"Benesch","year":"2015","journal-title":"Journal of Diabetes Science and Technology"},{"key":"2023010809171793800_bib32","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1111\/j.1463-1326.2011.01549.x","article-title":"Impaired incretin effect and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity","volume":"14","author":"Knop","year":"2012","journal-title":"Diabetes, Obesity and Metabolism"},{"key":"2023010809171793800_bib33","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1007\/s00125-007-0598-z","article-title":"Suppression of glucagon secretion is lower after oral glucose administration than during intravenous glucose administration in human subjects","volume":"50","author":"Meier","year":"2007","journal-title":"Diabetologia"},{"key":"2023010809171793800_bib34","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1007\/s00125-009-1511-8","article-title":"Resolution of type 2 diabetes following gastric bypass surgery: involvement of gut-derived glucagon and glucagonotropic signalling?","volume":"52","author":"Knop","year":"2009","journal-title":"Diabetologia"},{"key":"2023010809171793800_bib35","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1210\/jc.2010-2435","article-title":"Impaired regulation of the incretin effect in patients with type 2 diabetes","volume":"96","author":"Bagger","year":"2011","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"2023010809171793800_bib36","doi-asserted-by":"crossref","first-page":"884","DOI":"10.2337\/dc16-0351","article-title":"Roles of the gut in glucose homeostasis","volume":"39","author":"Holst","year":"2016","journal-title":"Diabetes Care"},{"key":"2023010809171793800_bib37","doi-asserted-by":"crossref","first-page":"161","DOI":"10.2337\/dc19-1328","article-title":"Efficacy and safety of the glucagon receptor antagonist RVT-1502 in type 2 diabetes uncontrolled on metformin monotherapy: a 12-week dose-ranging study","volume":"43","author":"Pettus","year":"2020","journal-title":"Diabetes Care"},{"key":"2023010809171793800_bib38","first-page":"E93","article-title":"Disruption of glucagon receptor signaling causes hyperaminoacidemia exposing a possible liver-alpha-cell axis","volume":"314","author":"Galsgaard","year":"2018","journal-title":"American Journal of Physiology: Endocrinology and Metabolism"},{"key":"2023010809171793800_bib39","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1210\/er.2006-0007","article-title":"\u03b1-Cells of the endocrine pancreas: 35 years of research but the enigma remains","volume":"28","author":"Gromada","year":"2007","journal-title":"Endocrine Reviews"},{"key":"2023010809171793800_bib40","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.peptides.2016.12.012","article-title":"Glucagon increases insulin levels by stimulating insulin secretion without effect on insulin clearance in mice","volume":"88","author":"Song","year":"2017","journal-title":"Peptides"},{"key":"2023010809171793800_bib41","doi-asserted-by":"crossref","first-page":"1127.e2","DOI":"10.1016\/j.celrep.2018.10.018","article-title":"Insulin secretion depends on intra-islet glucagon signaling","volume":"25","author":"Svendsen","year":"2018","journal-title":"Cell Reports"},{"key":"2023010809171793800_bib42","doi-asserted-by":"crossref","first-page":"e127994","DOI":"10.1172\/jci.insight.127994","article-title":"Intraislet glucagon signaling is critical for maintaining glucose homeostasis","volume":"5","author":"Zhu","year":"2019","journal-title":"JCI Insight"},{"key":"2023010809171793800_bib43","doi-asserted-by":"crossref","first-page":"e126742","DOI":"10.1172\/jci.insight.126742","article-title":"\u03b2 Cell tone is defined by proglucagon peptides through cAMP signaling","volume":"4","author":"Capozzi","year":"2019","journal-title":"JCI Insight"},{"key":"2023010809171793800_bib44","doi-asserted-by":"crossref","first-page":"86","DOI":"10.2337\/diabetes.48.1.86","article-title":"Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans: studies with the antagonist exendin 9\u201339","volume":"48","author":"Edwards","year":"1999","journal-title":"Diabetes"},{"key":"2023010809171793800_bib45","doi-asserted-by":"crossref","first-page":"906","DOI":"10.2337\/db18-1123","article-title":"Separate and combined glucometabolic effects of endogenous glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 in healthy individuals","volume":"68","author":"Gasbjerg","year":"2019","journal-title":"Diabetes"},{"key":"2023010809171793800_bib46","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/BF00400639","article-title":"Failure of glucagon suppression contributes to postprandial hyperglycaemia in IDDM","volume":"38","author":"Dinneen","year":"1995","journal-title":"Diabetologia"},{"key":"2023010809171793800_bib47","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1152\/physrev.00063.2017","article-title":"Mechanisms of insulin action and insulin resistance","volume":"98","author":"Petersen","year":"2018","journal-title":"Physiological Reviews"},{"key":"2023010809171793800_bib48","doi-asserted-by":"crossref","first-page":"532","DOI":"10.2337\/dbi19-0004","article-title":"Repositioning glucagon action in the physiology and pharmacology of diabetes","volume":"69","author":"Finan","year":"2020","journal-title":"Diabetes"},{"key":"2023010809171793800_bib49","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.2337\/dci15-0033","article-title":"Clinical trials, triumphs, and tribulations of glucagon receptor antagonists","volume":"39","author":"Pearson","year":"2016","journal-title":"Diabetes Care"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/187\/4\/EJE-22-0291.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/187\/4\/EJE-22-0291.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/187\/4\/507\/48515749\/eje-22-0291.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/187\/4\/507\/48515749\/eje-22-0291.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T23:14:09Z","timestamp":1727824449000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/187\/4\/507\/6972062"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,16]]},"references-count":49,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,10,1]]}},"URL":"https:\/\/doi.org\/10.1530\/eje-22-0291","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"type":"print","value":"0804-4643"},{"type":"electronic","value":"1479-683X"}],"subject":[],"published-other":{"date-parts":[[2022,10]]},"published":{"date-parts":[[2022,9,16]]}}}