{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:30:46Z","timestamp":1790685046818,"version":"4.1.0"},"reference-count":73,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T00:00:00Z","timestamp":1574985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870527"],"award-info":[{"award-number":["81870527"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670700"],"award-info":[{"award-number":["81670700"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Municipal Education Commission \u2014Gaofeng Clinical Medicine","award":["20172006"],"award-info":[{"award-number":["20172006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Beta-cell dedifferentiation was recently proposed as a mechanism of \u03b2-cell dysfunction, but whether it can be a trigger of \u03b2-cell failure preceding hyperglycemia in humans is uncertain. Pancreatic cancer can cause new-onset diabetes, yet the underlying mechanism is unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To investigate whether \u03b2-cell dedifferentiation is present in nondiabetic pancreatic ductal adenocarcinoma (PDAC) patients, we examined pancreatic islets from 15 nondiabetic patients with benign tumors (control) and 15 nondiabetic PDAC patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>We calculated the number of hormone-negative endocrine cells and evaluated important markers of \u03b2-cell dedifferentiation and function in the paraneoplastic islets. We assessed tumor-related inflammatory changes under the pancreatic cancer microenvironment and their influence on \u03b2-cell identity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We found nearly 10% of nonhormone expressing endocrine cells in nondiabetic PDAC subjects. The PDAC islets were dysfunctional, evidenced by low expression of Glucose transporter 2 (GLUT2) and Urocortin3 (UCN3), and concomitant upregulation of Aldehyde Dehydrogenase 1 Family Member A3 (ALDH1A3) expression and proinsulin accumulation. Pancreatic cancer caused paraneoplastic inflammation with enhanced tissue fibrosis, monocytes\/macrophages infiltration, and elevated inflammatory cytokines. Moreover, we detected \u03b2-cell dedifferentiation and defects in GSIS in islets exposed to PANC-1 (a cell line established from a pancreatic carcinoma of ductal origin from a 56-year-old Caucasian male)-conditioned medium. In a larger cohort, we showed high prevalence of new-onset diabetes in PDAC subjects, and fasting blood glucose (FBG) was found to be an additional useful parameter for early diagnosis of PDAC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our data provide a rationale for \u03b2-cell dedifferentiation in the pathogenesis of pancreatic cancer\u2013associated diabetes. We propose that \u03b2-cell dedifferentiation can be a trigger for \u03b2-cell failure in humans, before hyperglycemia occurs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgz224","type":"journal-article","created":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T05:30:43Z","timestamp":1575005443000},"page":"e1489-e1503","source":"Crossref","is-referenced-by-count":27,"title":["Paraneoplastic \u03b2 Cell Dedifferentiation in Nondiabetic Patients with Pancreatic Cancer"],"prefix":"10.1210","volume":"105","author":[{"given":"Yichen","family":"Wang","sequence":"first","affiliation":[{"name":"Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commision of the PR China, Shanghai Institute of Endocrine and Metabolic Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Xu","sequence":"additional","affiliation":[{"name":"Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commision of the PR China, Shanghai Institute of Endocrine and Metabolic Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 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