{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T23:09:25Z","timestamp":1776121765241,"version":"3.50.1"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pancreatic \u03b2-cell loss through apoptosis is an important disease mechanism in type 2 diabetes. Apoptosis Repressor with CARD (ARC) is a cell death inhibitor that antagonizes multiple death programs. We previously reported that ARC is abundant in pancreatic \u03b2-cells and modulates survival of these cells <jats:italic>in vitro<\/jats:italic>. Herein we assessed the importance of endogenous ARC in maintaining islet structure and function <jats:italic>in vivo<\/jats:italic>. While generalized loss of ARC did not result in detectable abnormalities, its absence in <jats:italic>ob\/ob<\/jats:italic> mice, a model of type 2 diabetes, induced a striking pancreatic phenotype: marked \u03b2-cell death, loss of \u03b2-cell mass, derangements of islet architecture, and impaired glucose-stimulated insulin secretion <jats:italic>in vivo<\/jats:italic>. These abnormalities contributed to worsening of hyperglycemia and glucose-intolerance in these mice. Mechanistically, the absence of ARC increased levels of C\/EBP homologous protein (CHOP) in wild type isolated islets stimulated with ER stress and in <jats:italic>ob\/ob<\/jats:italic> isolated islets at baseline. Deletion of CHOP in <jats:italic>ob\/ob<\/jats:italic>; ARC \u2212\/\u2212 mice led to reversal of \u03b2-cell death and abnormalities in islet architecture. These data indicate that suppression of CHOP by endogenous levels of ARC is critical for \u03b2-cell viability and maintenance of normal islet structure in this model of type 2 diabetes.<\/jats:p>","DOI":"10.1038\/s41598-017-07107-w","type":"journal-article","created":{"date-parts":[[2017,7,26]],"date-time":"2017-07-26T16:10:43Z","timestamp":1501085443000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["ARC is essential for maintaining pancreatic islet structure and \u03b2-cell viability during type 2 diabetes"],"prefix":"10.1038","volume":"7","author":[{"given":"Wendy M.","family":"McKimpson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Streamson C.","family":"Chua","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey E.","family":"Pessin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1395-9694","authenticated-orcid":false,"given":"Richard N.","family":"Kitsis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,8,1]]},"reference":[{"key":"7107_CR1","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1210\/jc.2014-1425","volume":"99","author":"PA Halban","year":"2014","unstructured":"Halban, P. 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