{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T01:20:11Z","timestamp":1780536011135,"version":"3.54.1"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2016,4,25]],"date-time":"2016-04-25T00:00:00Z","timestamp":1461542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008871","name":"JDRF","doi-asserted-by":"publisher","award":["17-2012-588"],"award-info":[{"award-number":["17-2012-588"]}],"id":[{"id":"10.13039\/100008871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008871","name":"JDRF","doi-asserted-by":"publisher","award":["1-PNF-2014-96-Q-R"],"award-info":[{"award-number":["1-PNF-2014-96-Q-R"]}],"id":[{"id":"10.13039\/100008871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["8UL1TR000055"],"award-info":[{"award-number":["8UL1TR000055"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0152662","type":"journal-article","created":{"date-parts":[[2016,4,25]],"date-time":"2016-04-25T17:28:29Z","timestamp":1461605309000},"page":"e0152662","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":49,"title":["Circulating Differentially Methylated Amylin DNA as a Biomarker of \u03b2-Cell Loss in Type 1 Diabetes"],"prefix":"10.1371","volume":"11","author":[{"given":"John A.","family":"Olsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren A.","family":"Kenna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Spelios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Hessner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eitan M.","family":"Akirav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,4,25]]},"reference":[{"issue":"1","key":"ref1","doi-asserted-by":"crossref","first-page":"525","DOI":"10.4049\/jimmunol.163.1.525","article-title":"Early autoantibody responses in prediabetes are IgG1 dominated and suggest antigen-specific regulation","volume":"163","author":"E Bonifacio","year":"1999","journal-title":"Journal of immunology"},{"issue":"7","key":"ref2","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nrg3230","article-title":"Functions of DNA methylation: islands, start sites, gene bodies and beyond","volume":"13","author":"PA Jones","year":"2012","journal-title":"Nature reviews Genetics"},{"issue":"9","key":"ref3","doi-asserted-by":"crossref","first-page":"e6953","DOI":"10.1371\/journal.pone.0006953","article-title":"Insulin gene expression is regulated by DNA methylation","volume":"4","author":"A Kuroda","year":"2009","journal-title":"PloS one"},{"issue":"18","key":"ref4","doi-asserted-by":"crossref","first-page":"9821","DOI":"10.1073\/pnas.93.18.9821","article-title":"Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands","volume":"93","author":"JG Herman","year":"1996","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"9","key":"ref5","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1038\/nm0996-1035","article-title":"Microsatellite alterations in serum DNA of head and neck cancer patients","volume":"2","author":"H Nawroz","year":"1996","journal-title":"Nature medicine"},{"issue":"9","key":"ref6","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1038\/nm0996-1033","article-title":"Microsatellite alterations in plasma DNA of small cell lung cancer patients","volume":"2","author":"XQ Chen","year":"1996","journal-title":"Nature medicine"},{"issue":"8","key":"ref7","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/nrclinonc.2013.110","article-title":"Liquid biopsy: monitoring cancer-genetics in the blood","volume":"10","author":"E Crowley","year":"2013","journal-title":"Nature reviews Clinical oncology"},{"issue":"47","key":"ref8","doi-asserted-by":"crossref","first-page":"19018","DOI":"10.1073\/pnas.1111008108","article-title":"Detection of beta cell death in diabetes using differentially methylated circulating DNA","volume":"108","author":"EM Akirav","year":"2011","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"10","key":"ref9","doi-asserted-by":"crossref","first-page":"e47942","DOI":"10.1371\/journal.pone.0047942","article-title":"Development of a quantitative methylation-specific polymerase chain reaction method for monitoring beta cell death in type 1 diabetes","volume":"7","author":"MI Husseiny","year":"2012","journal-title":"PloS one"},{"issue":"5","key":"ref10","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.2337\/db12-1207","article-title":"Immune therapy and beta-cell death in type 1 diabetes","volume":"62","author":"J Lebastchi","year":"2013","journal-title":"Diabetes"},{"key":"ref11","article-title":"Elevations in Circulating Methylated and Unmethylated Preproinsulin DNA in New-Onset Type 1 Diabetes","author":"MM Fisher","year":"2015","journal-title":"Diabetes"},{"issue":"3","key":"ref12","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1172\/JCI78142","article-title":"beta cell death and dysfunction during type 1 diabetes development in at-risk individuals","volume":"125","author":"KC Herold","year":"2015","journal-title":"The Journal of clinical investigation"},{"issue":"11","key":"ref13","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1007\/BF00274799","article-title":"Islet amyloid polypeptide-like immunoreactivity in the islet B cells of type 2 (non-insulin-dependent) diabetic and non-diabetic individuals","volume":"30","author":"P Westermark","year":"1987","journal-title":"Diabetologia"},{"issue":"9","key":"ref14","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.1073\/pnas.86.9.3127","article-title":"Rat amylin: cloning and tissue-specific expression in pancreatic islets","volume":"86","author":"JD Leffert","year":"1989","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"4","key":"ref15","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1007\/BF00285291","article-title":"Co-localization of islet amyloid polypeptide and insulin in the B cell secretory granules of the human pancreatic islets","volume":"32","author":"A Lukinius","year":"1989","journal-title":"Diabetologia"},{"issue":"5","key":"ref16","doi-asserted-by":"crossref","first-page":"634","DOI":"10.2337\/diab.39.5.634","article-title":"Evidence of cosecretion of islet amyloid polypeptide and insulin by beta-cells","volume":"39","author":"SE Kahn","year":"1990","journal-title":"Diabetes"},{"issue":"12","key":"ref17","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.2337\/diab.40.12.1701","article-title":"Islet amyloid polypeptide and insulin secretion from isolated perfused pancreas of fed, fasted, glucose-treated, and dexamethasone-treated rats","volume":"40","author":"TD O'Brien","year":"1991","journal-title":"Diabetes"},{"issue":"1\u20132","key":"ref18","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0014-5793(90)80365-P","article-title":"IAPP\/amylin gene transcriptional control region: evidence for negative regulation","volume":"271","author":"S Mosselman","year":"1990","journal-title":"FEBS letters"},{"issue":"4","key":"ref19","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1128\/MCB.12.4.1777","article-title":"The insulin and islet amyloid polypeptide genes contain similar cell-specific promoter elements that bind identical beta-cell nuclear complexes","volume":"12","author":"MS German","year":"1992","journal-title":"Molecular and cellular biology"},{"issue":"Pt 2","key":"ref20","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1042\/bj3130495","article-title":"Insulin upstream factor 1 and a novel ubiquitous factor bind to the human islet amyloid polypeptide\/amylin gene promoter","volume":"313","author":"D Bretherton-Watt","year":"1996","journal-title":"The Biochemical journal"},{"issue":"11","key":"ref21","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.1073\/pnas.84.11.3881","article-title":"Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells","volume":"84","author":"P Westermark","year":"1987","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"4","key":"ref22","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1006\/jmbi.1999.3422","article-title":"Identification of a penta- and hexapeptide of islet amyloid polypeptide (IAPP) with amyloidogenic and cytotoxic properties","volume":"295","author":"K Tenidis","year":"2000","journal-title":"Journal of molecular biology"},{"issue":"3","key":"ref23","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1152\/physrev.00042.2009","article-title":"Islet amyloid polypeptide, islet amyloid, and diabetes mellitus","volume":"91","author":"P Westermark","year":"2011","journal-title":"Physiological reviews"},{"issue":"4","key":"ref24","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1046\/j.1365-2362.2003.01142.x","article-title":"Inverse relation between amylin and glucagon secretion in healthy and diabetic human subjects","volume":"33","author":"B Ludvik","year":"2003","journal-title":"European journal of clinical investigation"},{"issue":"1","key":"ref25","doi-asserted-by":"crossref","first-page":"R114","DOI":"10.1152\/ajpregu.00333.2003","article-title":"The anorectic hormone amylin contributes to feeding-related changes of neuronal activity in key structures of the gut-brain axis","volume":"286","author":"T Riediger","year":"2004","journal-title":"American journal of physiology Regulatory, integrative and comparative physiology"},{"issue":"3","key":"ref26","doi-asserted-by":"crossref","first-page":"R568","DOI":"10.1152\/ajpregu.00213.2004","article-title":"Amylin receptor blockade stimulates food intake in rats","volume":"287","author":"RD Reidelberger","year":"2004","journal-title":"American journal of physiology Regulatory, integrative and comparative physiology"},{"issue":"9","key":"ref27","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1055\/s-2002-34790","article-title":"The human amylin analog, pramlintide, reduces postprandial hyperglucagonemia in patients with type 2 diabetes mellitus","volume":"34","author":"M Fineman","year":"2002","journal-title":"Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme"},{"issue":"3","key":"ref28","doi-asserted-by":"crossref","first-page":"784","DOI":"10.2337\/diacare.26.3.784","article-title":"Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-year randomized controlled trial","volume":"26","author":"PA Hollander","year":"2003","journal-title":"Diabetes care"},{"issue":"4","key":"ref29","doi-asserted-by":"crossref","first-page":"724","DOI":"10.2337\/diacare.25.4.724","article-title":"A randomized study and open-label extension evaluating the long-term efficacy of pramlintide as an adjunct to insulin therapy in type 1 diabetes","volume":"25","author":"F Whitehouse","year":"2002","journal-title":"Diabetes care"},{"issue":"10","key":"ref30","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1016\/j.clinthera.2005.10.009","article-title":"Pramlintide in the treatment of type 1 and type 2 diabetes mellitus","volume":"27","author":"GJ Ryan","year":"2005","journal-title":"Clinical therapeutics"},{"issue":"3","key":"ref31","doi-asserted-by":"crossref","first-page":"876","DOI":"10.2337\/db10-0793","article-title":"Glucose and inflammation control islet vascular density and beta-cell function in NOD mice: control of islet vasculature and vascular endothelial growth factor by glucose","volume":"60","author":"EM Akirav","year":"2011","journal-title":"Diabetes"},{"key":"ref32","article-title":"Islet endothelial cells induce glycosylation and increase cell-surface expression of integrin beta1 in beta-cells","author":"MG Spelios","year":"2015","journal-title":"The Journal of biological chemistry"},{"issue":"8","key":"ref33","doi-asserted-by":"crossref","first-page":"e72260","DOI":"10.1371\/journal.pone.0072260","article-title":"In vitro formation of beta cell pseudoislets using islet-derived endothelial cells","volume":"8","author":"MG Spelios","year":"2013","journal-title":"PloS one"},{"issue":"9","key":"ref34","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.1172\/JCI58447","article-title":"A genetically engineered human pancreatic beta cell line exhibiting glucose-inducible insulin secretion","volume":"121","author":"P Ravassard","year":"2011","journal-title":"The Journal of clinical investigation"},{"issue":"4","key":"ref35","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s00125-009-1259-1","article-title":"A simple two-step protocol for the purification of human pancreatic beta cells","volume":"52","author":"M Banerjee","year":"2009","journal-title":"Diabetologia"},{"issue":"7","key":"ref36","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S","article-title":"Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation","volume":"15","author":"KG Alberti","year":"1998","journal-title":"Diabet Med"},{"issue":"11","key":"ref37","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.2337\/db07-1817","article-title":"Beta-cell mass and type 1 diabetes: going, going, gone?","volume":"57","author":"E Akirav","year":"2008","journal-title":"Diabetes"},{"issue":"10","key":"ref38","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.2337\/db11-0844","article-title":"Immune regulatory properties of allogeneic adipose-derived mesenchymal stem cells in the treatment of experimental autoimmune diabetes","volume":"61","author":"EJ Bassi","year":"2012","journal-title":"Diabetes"},{"issue":"3","key":"ref39","doi-asserted-by":"crossref","first-page":"e93053","DOI":"10.1371\/journal.pone.0093053","article-title":"High plasma levels of islet amyloid polypeptide in young with new-onset of type 1 diabetes mellitus","volume":"9","author":"JF Paulsson","year":"2014","journal-title":"PloS one"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0152662","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T19:32:41Z","timestamp":1692300761000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0152662"}},"subtitle":[],"editor":[{"given":"Rohit","family":"Kulkarni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,4,25]]},"references-count":39,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2016,4,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0152662","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,25]]}}}