{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T03:20:26Z","timestamp":1791602426151,"version":"4.3.4"},"reference-count":21,"publisher":"Bioscientifica","issue":"8","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:p>\n                    Glucagon cell hyperplasia and neoplasia (GCHN) is the name of an endocrine receptor disease, whose morphology was first described in 2006. Three years later, this rare disease was found to be to be caused by an inactivating mutation of the glucagon receptor (\n                    <jats:italic>GCGR<\/jats:italic>\n                    ) gene. Functionally, the genetic defect mainly affects glucagon signaling in the liver with changes in the metabolism of glycogen, fatty acids and amino acids. Recent results of several studies in\n                    <jats:italic>GCGR<\/jats:italic>\n                    knockout mice suggested that elevated serum amino acid levels probably stimulate glucagon cell hyperplasia with subsequent transformation into glucagon cell neoplasia. This process leads over time to numerous small and some large pancreatic neuroendocrine tumors which are potentially malignant. Despite high glucagon serum levels, the patients develop no glucagonoma syndrome. In 2015, GCHN was identified as an autosomal recessive hereditary disorder.\n                  <\/jats:p>","DOI":"10.1530\/erc-23-0032","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T09:33:02Z","timestamp":1685611982000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":11,"title":["Glucagon cell hyperplasia and neoplasia: a recently recognized endocrine receptor disease"],"prefix":"10.1530","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7311-3343","authenticated-orcid":true,"given":"Bence","family":"Sipos","sequence":"first","affiliation":[{"name":"Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tubingen, T\u00fcbingen, Germany"},{"name":"ENETS Center of Excellence, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnter","family":"Kl\u00f6ppel","sequence":"additional","affiliation":[{"name":"Department of Pathology, Technical University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"American Journal of Surgical Pathology","first-page":"560","article-title":"Microadenomatosis of the endocrine pancreas in patients with and without the multiple endocrine neoplasia type 1 syndrome","volume":"30","author":"Anlauf","year":"2006","unstructured":"Anlauf MSchlenger RPerren ABauersfeld JKoch CADralle HRaffel AKnoefel WTWeihe ERuszniewski P, 2006Microadenomatosis of the endocrine pancreas in patients with and without the multiple endocrine neoplasia type 1 syndrome. American Journal of Surgical Pathology30560\u2013574. (https:\/\/doi.org\/10.1097\/01.pas.0000194044.01104.25)16699310"},{"key":"bib2","series-title":"Cell Metabolism","first-page":"1654","article-title":"The past, present, and future physiology and pharmacology of glucagon","volume":"34","author":"Capozzi","year":"2022","unstructured":"Capozzi MED'Alessio DA & Campbell JE2022The past, present, and future physiology and pharmacology of glucagon. Cell Metabolism341654\u20131674. (https:\/\/doi.org\/10.1016\/j.cmet.2022.10.001)36323234"},{"key":"bib3","series-title":"Proceedings of the National Academy of Sciences of the United States of America","first-page":"1438","article-title":"Lower blood glucose, hyperglucagonemia, and pancreatic \u03b1 cell hyperplasia in glucagon receptor knockout mice","volume":"100","author":"Gelling","year":"2003","unstructured":"Gelling RWDu XQDichmann DSRomer JHuang HCui LObici STang BHolst JJFledelius C, 2003Lower blood glucose, hyperglucagonemia, and pancreatic \u03b1 cell hyperplasia in glucagon receptor knockout mice. Proceedings of the National Academy of Sciences of the United States of America1001438\u20131443. (https:\/\/doi.org\/10.1073\/pnas.0237106100)12552113"},{"key":"bib4","series-title":"Diabetes, Obesity and Metabolism","first-page":"1521","article-title":"Treatment with LY2409021, a glucagon receptor antagonist, increases liver fat in patients with type 2 diabetes","volume":"19","author":"Guzman","year":"2017","unstructured":"Guzman CBZhang XMLiu RRegev AShankar SGarhyan PPillai SGKazda CChalasani N & Hardy TA.2017Treatment with LY2409021, a glucagon receptor antagonist, increases liver fat in patients with type 2 diabetes. Diabetes, Obesity and Metabolism191521\u20131528. (https:\/\/doi.org\/10.1111\/dom.12958)28371155"},{"key":"bib5","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"213","article-title":"Glucagon cell adenomatosis: a newly recognized disease of the endocrine pancreas","volume":"94","author":"Henopp","year":"2009","unstructured":"Henopp TAnlauf MSchmitt ASchlenger RZalatnai ACouvelard ARuszniewski PSchaps KPJonkers YMSpeel EJ, 2009Glucagon cell adenomatosis: a newly recognized disease of the endocrine pancreas. Journal of Clinical Endocrinology and Metabolism94213\u2013217. (https:\/\/doi.org\/10.1210\/jc.2008-1300)18957496"},{"key":"bib6","series-title":"International Journal of Molecular Sciences","article-title":"Glucagon receptor signaling and glucagon resistance","volume":"20","author":"Janah","year":"2019","unstructured":"Janah LKjeldsen SGalsgaard KDWinther-S\u00f8rensen MStojanovska EPedersen JKnop FKHolst JJ & Wewer Albrechtsen NJ2019Glucagon receptor signaling and glucagon resistance. International Journal of Molecular Sciences20 3314. (https:\/\/doi.org\/10.3390\/ijms20133314)"},{"key":"bib7","series-title":"Endocrinology","first-page":"979","article-title":"Increased SLC38A4 amino acid transporter expression in human pancreatic \u03b1-cells after glucagon receptor inhibition","volume":"160","author":"Kim","year":"2019","unstructured":"Kim JDominguez Gutierrez GXin YCavino KSung BSipos BKloeppel GGromada J & Okamoto H2019Increased SLC38A4 amino acid transporter expression in human pancreatic \u03b1-cells after glucagon receptor inhibition. Endocrinology160979\u2013988. (https:\/\/doi.org\/10.1210\/en.2019-00022)30938753"},{"key":"bib8","series-title":"Cell Metabolism","first-page":"1348","article-title":"Amino acid transporter Slc38a5 controls glucagon receptor inhibition-induced pancreatic \u03b1 cell hyperplasia in mice","volume":"25","author":"Kim","year":"2017","unstructured":"Kim JOkamoto HHuang ZAnguiano GChen SLiu QCavino KXin YNa EHamid R, 2017Amino acid transporter Slc38a5 controls glucagon receptor inhibition-induced pancreatic \u03b1 cell hyperplasia in mice. Cell Metabolism251348\u20131361.e8. (https:\/\/doi.org\/10.1016\/j.cmet.2017.05.006)28591637"},{"key":"bib9","series-title":"Endocrinology, Diabetes and Metabolism Case Reports","first-page":"16","article-title":"Pancreatic \u03b1-cell hyperplasia and hyperglucagonemia due to a glucagon receptor splice mutation","volume":"2016","author":"Larger","year":"2016","unstructured":"Larger EWewer Albrechtsen NJHansen LHGelling RWCapeau JDeacon CFMadsen ODYakushiji FDe Meyts PHolst JJ, 2016Pancreatic \u03b1-cell hyperplasia and hyperglucagonemia due to a glucagon receptor splice mutation. Endocrinology, Diabetes and Metabolism Case Reports201616\u20130081. (https:\/\/doi.org\/10.1530\/EDM-16-0081)27933176"},{"key":"bib10","series-title":"Molecular Genetics and Metabolism Reports","first-page":"46","article-title":"The first pediatric case of glucagon receptor defect due to biallelic mutations in GCGR is identified by newborn screening of elevated arginine","volume":"17","author":"Li","year":"2018","unstructured":"Li HZhao LSingh RHam JNFadoju DOBean LJHZhang YXu YXu HE & Gambello MJ2018The first pediatric case of glucagon receptor defect due to biallelic mutations in GCGR is identified by newborn screening of elevated arginine. Molecular Genetics and Metabolism Reports1746\u201352. (https:\/\/doi.org\/10.1016\/j.ymgmr.2018.09.006)30294546"},{"key":"bib21","first-page":"2581","year":"2020","unstructured":"Lin GLiu QDai ACai XZhou QWang XChen YYe CLi JYang DWang MW2020 Characterization of a naturally occurring mutation V368M in the human glucagon receptor and its association with metabolic disorders. Biochemical Journal4772581\u20132594. (https:\/\/doi.org\/10.1042\/bcj20200235)"},{"key":"bib11","series-title":"Journal of the American Academy of Dermatology","first-page":"458","article-title":"Glucagon cell adenomatosis: a new entity associated with necrolytic migratory erythema and glucagonoma syndrome","volume":"65","author":"Otto","year":"2011","unstructured":"Otto AIMarschalko MZalatnai AToth MKovacs JHarsing JTulassay Z & Karpati S2011Glucagon cell adenomatosis: a new entity associated with necrolytic migratory erythema and glucagonoma syndrome. Journal of the American Academy of Dermatology65458\u2013459. (https:\/\/doi.org\/10.1016\/j.jaad.2010.04.010)21763589"},{"key":"bib12","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"E783","article-title":"Glucagon cell hyperplasia and neoplasia with and without glucagon receptor mutations","volume":"100","author":"Sipos","year":"2015","unstructured":"Sipos BSperveslage JAnlauf MHoffmeister MHenopp TBuch SHampe JWeber AHammel PCouvelard A, 2015Glucagon cell hyperplasia and neoplasia with and without glucagon receptor mutations. Journal of Clinical Endocrinology and Metabolism100E783\u2013E788. (https:\/\/doi.org\/10.1210\/jc.2014-4405)25695890"},{"key":"bib13","series-title":"Cell Reports","first-page":"495","article-title":"Glucagon couples hepatic amino acid catabolism to mTOR-dependent regulation of \u03b1-cell Mass.","volume":"12","author":"Solloway","year":"2015","unstructured":"Solloway MJMadjidi AGu CEastham-Anderson JClarke HJKljavin NZavala-Solorio JKates LFriedman BBrauer M, 2015Glucagon couples hepatic amino acid catabolism to mTOR-dependent regulation of \u03b1-cell Mass.Cell Reports12495\u2013510. (https:\/\/doi.org\/10.1016\/j.celrep.2015.06.034)26166562"},{"key":"bib19","series-title":"Neuroendocrinology","article-title":"A novel hereditary pancreatic neuroendocrine tumor syndrome associated with biallelic inactivation of the glucagon receptor","volume":"103","year":"2016","unstructured":"Tang L & Yu R2016A novel hereditary pancreatic neuroendocrine tumor syndrome associated with biallelic inactivation of the glucagon receptor. Neuroendocrinology103(Suppl 1) abstract B11. (https:\/\/doi.org\/10.1159\/000448725)"},{"key":"bib14","series-title":"Journal of Biological Chemistry","article-title":"Molecular and in vivo phenotyping of missense variants of the human glucagon receptor","volume":"298","author":"van der Velden","year":"2022","unstructured":"van der Velden WJCLindquist PMadsen JSStassen RHMJWewer Albrechtsen NJHolst JJHauser AS & Rosenkilde MM2022Molecular and in vivo phenotyping of missense variants of the human glucagon receptor. Journal of Biological Chemistry298 101413. (https:\/\/doi.org\/10.1016\/j.jbc.2021.101413)34801547"},{"key":"bib15","series-title":"WHO\/IARC Classification of Tumours","year":"2018","unstructured":"WHO Classification of Tumours of Endocrine Organs2018WHO\/IARC Classification of Tumours, 4th ed. Eds. LloydRV, OsamuraRY, Kl\u00f6ppelG, RosaiJ & YuR. Lyon, France: IARCPublications."},{"key":"bib16","series-title":"Pancreas","first-page":"428","article-title":"Nesidioblastosis and hyperplasia of alpha cells, microglucagonoma, and nonfunctioning islet cell tumor of the pancreas: review of the literature","volume":"36","author":"Yu","year":"2008","unstructured":"Yu RNissen NNDhall D & Heaney AP2008Nesidioblastosis and hyperplasia of alpha cells, microglucagonoma, and nonfunctioning islet cell tumor of the pancreas: review of the literature. Pancreas36428\u2013431. (https:\/\/doi.org\/10.1097\/MPA.0b013e31815ceb23)18437091"},{"key":"bib20","series-title":"Neuroendocrinology","article-title":"Characterization and rescue of a pathogenic D63N mutant human glucagon receptor that causes a pancreatic neuroendocrine tumor syndrome (Mahvash disease)","volume":"103","year":"2016","unstructured":"Yu RZhou CChen CR2016Characterization and rescue of a pathogenic D63N mutant human glucagon receptor that causes a pancreatic neuroendocrine tumor syndrome (Mahvash disease). Neuroendocrinology103(Suppl 1) abstract B13. (https:\/\/doi.org\/10.1159\/000448725)"},{"key":"bib18","series-title":"Pancreas","first-page":"511","article-title":"Mahvash disease: 10 years after discovery","volume":"47","year":"2018","unstructured":"Yu R2018Mahvash disease: 10 years after discovery. Pancreas47511\u2013515. (https:\/\/doi.org\/10.1097\/mpa.0000000000001044)29702528"},{"key":"bib17","series-title":"Pancreas","first-page":"941","article-title":"Homozygous P86S mutation of the human glucagon receptor is associated with hyperglucagonemia, alpha cell hyperplasia, and islet cell tumor","volume":"38","author":"Zhou","year":"2009","unstructured":"Zhou CDhall DNissen NNChen CR & Yu R2009Homozygous P86S mutation of the human glucagon receptor is associated with hyperglucagonemia, alpha cell hyperplasia, and islet cell tumor. Pancreas38941\u2013946. (https:\/\/doi.org\/10.1097\/MPA.0b013e3181b2bb03)19657311"}],"container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/30\/8\/ERC-23-0032.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/30\/8\/ERC-23-0032.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/30\/8\/ERC-23-0032.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:56:33Z","timestamp":1784555793000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/25740"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,1]]},"references-count":21,"journal-issue":{"issue":"8"},"URL":"https:\/\/doi.org\/10.1530\/erc-23-0032","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,1]]}}}