{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T05:37:52Z","timestamp":1767937072054,"version":"3.49.0"},"reference-count":24,"publisher":"American Diabetes Association","issue":"9","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"vor","delay-in-days":306,"URL":"http:\/\/www.diabetesjournals.org\/site\/license"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT088566"],"award-info":[{"award-number":["WT088566"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT097820"],"award-info":[{"award-number":["WT097820"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["DTP Studentship"],"award-info":[{"award-number":["DTP Studentship"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["Rare Disease funding"],"award-info":[{"award-number":["Rare Disease funding"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,9,1]]},"abstract":"<jats:p>Diffuse congenital hyperinsulinism in infancy (CHI-D) arises from mutations inactivating the KATP channel; however, the phenotype is difficult to explain from electrophysiology alone. Here we studied wider abnormalities in the \u03b2-cell and other pancreatic lineages. Islets were disorganized in CHI-D compared with controls. PAX4 and ARX expression was decreased. A tendency toward increased NKX2.2 expression was consistent with its detection in two-thirds of CHI-D \u03b4-cell nuclei, similar to the fetal pancreas, and implied immature \u03b4-cell function. CHI-D \u03b4-cells also comprised 10% of cells displaying nucleomegaly. In CHI-D, increased proliferation was most elevated in duct (5- to 11-fold) and acinar (7- to 47-fold) lineages. Increased \u03b2-cell proliferation observed in some cases was offset by an increase in apoptosis; this is in keeping with no difference in INSULIN expression or surface area stained for insulin between CHI-D and control pancreas. However, nuclear localization of CDK6 and P27 was markedly enhanced in CHI-D \u03b2-cells compared with cytoplasmic localization in control cells. These combined data support normal \u03b2-cell mass in CHI-D, but with G1\/S molecules positioned in favor of cell cycle progression. New molecular abnormalities in \u03b4-cells and marked proliferative increases in other pancreatic lineages indicate CHI-D is not solely a \u03b2-cell disorder.<\/jats:p>","DOI":"10.2337\/db14-1202","type":"journal-article","created":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T01:22:19Z","timestamp":1430443339000},"page":"3182-3188","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":22,"title":["Altered Phenotype of \u03b2-Cells and Other Pancreatic Cell Lineages in Patients With Diffuse Congenital Hyperinsulinism in Infancy Caused by Mutations in the ATP-Sensitive K-Channel"],"prefix":"10.2337","volume":"64","author":[{"given":"Rachel J.","family":"Salisbury","sequence":"first","affiliation":[{"name":"Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Han","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, The University of Manchester, Manchester, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel E.","family":"Jennings","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, U.K."},{"name":"Department of Endocrinology, Central Manchester University Hospitals NHS Foundation Trust, Manchester, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew A.","family":"Berry","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Stevens","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, The University of Manchester, Manchester, U.K."},{"name":"Department of Paediatric Endocrinology, Central Manchester University Hospitals NHS Foundation Trust, Manchester, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zainab","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, The University of Manchester, Manchester, U.K."},{"name":"Department of Paediatric Endocrinology, Central Manchester University Hospitals NHS Foundation Trust, Manchester, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah A.","family":"Sugden","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald","family":"De Krijger","sequence":"additional","affiliation":[{"name":"Erasmus MC, Rotterdam, the Netherlands"},{"name":"Department of Pathology, Reinier de Graaf Hospital, Delft, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah E.","family":"Cross","sequence":"additional","affiliation":[{"name":"Diabetes Research & Wellness Foundation Human Islet Isolation Facility, Nuffield Department of Surgical Sciences and Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul P.V.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Diabetes Research & Wellness Foundation Human Islet Isolation Facility, Nuffield Department of Surgical Sciences and Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Newbould","sequence":"additional","affiliation":[{"name":"Department of Paediatric Histopathology, Central Manchester University Hospitals NHS Foundation Trust, Manchester, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen E.","family":"Cosgrove","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, The University of Manchester, Manchester, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen Piper","family":"Hanley","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Indraneel","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Centre for 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