{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:15:40Z","timestamp":1789172140688,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Insulin resistance and obesity\u2010associated inflammation are key drivers in the pathogenesis of Type 2 diabetes mellitus (T2DM). Whilst inflammatory cytokines are well known to impair \u03b2\u2010cell function, their impact on pancreatic \u03b1\u2010cells and glucagon (GCG) regulation remains poorly understood. In this study, we investigated the effects of the pro\u2010inflammatory cytokines interleukin (IL)\u20101\u03b2, tumour necrosis factor (TNF)\u2010\u03b1 and interferon (IFN)\u2010\u03b3 on GCG expression and secretion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>The viability and endocrine function of \u03b1\u2010cell line \u03b1TC1 and isolated islets were investigated by WST\u20101 assay, LDH assay, qRT\u2010PCR, Western blot analysis and ELISA. The transcriptional activity of the GCG promoter was analysed by reporter gene assays. The cellular composition of isolated islets was assessed by immunohistochemistry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that exposure of the \u03b1\u2010cell line \u03b1TC1 to a mix of these cytokines activates cellular stress responses characterised by induction of the nuclear factor kappa\u2010light\u2010chain\u2010enhancer of activated B\u2010cells (NF\u2010\u03baB) pathway and the nuclear factor erythroid 2\u2010related factor 2 (Nrf2) pathway. Moreover, cytokine treatment markedly reduced GCG gene expression and secretion through repression of GCG promoter activity. Mechanistically, this was associated with a disrupted transcriptional network. These findings were confirmed in isolated mouse islets, where cytokine exposure significantly reduced GCG expression and secretion in islets of both male and female donors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Taken together, these findings indicate that inflammatory cytokines are potent modulators of \u03b1\u2010cell function as well as GCG secretion and provide novel insights into inflammation\u2010driven dysregulation of the endocrine function of pancreatic islets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70921","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T01:38:21Z","timestamp":1780277901000},"page":"7149-7160","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammatory Cytokines Impair Glucagon Expression and Secretion in Pancreatic \u03b1\u2010Cells"],"prefix":"10.1111","volume":"28","author":[{"given":"Caroline","family":"Bickelmann","sequence":"first","affiliation":[{"name":"Institute for Clinical and Experimental Surgery, Saarland University, PharmaScienceHub (PSH)  Homburg Germany"},{"name":"Center for Gender Specific Biology and Medicine (CGBM) Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric","family":"Wilden","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Surgery, Saarland University, PharmaScienceHub (PSH)  Homburg Germany"},{"name":"Center for Gender Specific Biology and Medicine (CGBM) Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Prates\u2010Roma","sequence":"additional","affiliation":[{"name":"Center for Gender Specific Biology and Medicine (CGBM) Saarland University  Homburg Germany"},{"name":"Biophysics Department, Center for Human and Molecular Biology (ZHMB) Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias W.","family":"Laschke","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Surgery, Saarland University, PharmaScienceHub (PSH)  Homburg Germany"},{"name":"Center for Gender Specific Biology and Medicine (CGBM) Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1886-5657","authenticated-orcid":false,"given":"Emmanuel","family":"Ampofo","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Surgery, Saarland University, PharmaScienceHub (PSH)  Homburg Germany"},{"name":"Center for Gender Specific Biology and Medicine (CGBM) Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9134-8463","authenticated-orcid":false,"given":"Selina","family":"Wrublewsky","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Surgery, Saarland University, PharmaScienceHub (PSH)  Homburg Germany"},{"name":"Center for Gender Specific Biology and Medicine (CGBM) Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.116283"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26199715"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-025-01996-4"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06731-w"},{"issue":"8","key":"e_1_2_10_6_1","article-title":"Early Cytokine\u2010Induced Transient NOX2 Activity Is ER Stress\u2010Dependent and Impacts Beta\u2010Cell Function and Survival","volume":"10","author":"Vilas\u2010Boas E. 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