{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:18:50Z","timestamp":1784557130933,"version":"3.55.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"4","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,4,1]]},"abstract":"<jats:p>Strategies to increase functional pancreatic beta cell mass is of great interest in diabetes-related research. TNF-related apoptosis-inducing ligand (TRAIL) is well known to promote proliferation and survival in various cell types, including vascular smooth muscle and endothelial cells. Correlation between the protective nature of TRAIL on these cells and its proliferative effect is noteworthy. TRAIL\u2019s seemingly protective\/therapeutic effect in diabetes prompted us to question whether it may act as an inducer of proliferation in pancreatic beta cells. We used rat primary islet cells and MIN6 mouse beta cell line to investigate TRAIL-induced proliferation. Cell viability and\/or death was analyzed by MTT, WST-1, and Annexin-V\/PI assays, while proliferation rates and pathways were assessed via immunocytochemical and Western blot analyses. Receptor neutralization antibodies identified the mediator receptors. Recombinant soluble TRAIL (sTRAIL) treatment led to 1.6-fold increased proliferation in insulin-positive cells in dispersed rat islets compared to the untreated group, while adenovirus-mediated overexpression of TRAIL increased the number of proliferating beta cells up to more than six-fold. sTRAIL or adenoviral vector-mediated TRAIL overexpression induced proliferation in MIN6 cells also. TRAIL\u2019s proliferative effect was mediated via AKT activation, which was suppressed upon specific inhibition. Neutralization of each TRAIL receptor reversed the proliferative effect to some degree, with the highest level of inhibition in death receptor 5 (DR5) blockage in MIN6 cells and in decoy receptor 1 (DcR1) blockage in primary rat beta cells. Thus, TRAIL induces proliferation in rodent pancreatic beta cells through activation of the AKT pathway.<\/jats:p>","DOI":"10.1530\/jme-20-0037","type":"journal-article","created":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T03:04:25Z","timestamp":1618887865000},"page":"325-338","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":5,"title":["TRAIL induces proliferation in rodent pancreatic beta cells via AKT activation"],"prefix":"10.1530","volume":"66","author":[{"given":"Sevim","family":"Kahraman","sequence":"first","affiliation":[{"name":"1Center for Gene and Cell Therapy, Akdeniz University, Antalya, Turkey"},{"name":"2Department of Medical Biology and Genetics, Akdeniz University Faculty of Medicine, Antalya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozlem","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"1Center for Gene and Cell Therapy, Akdeniz University, Antalya, Turkey"},{"name":"2Department of Medical Biology and Genetics, Akdeniz University Faculty of Medicine, Antalya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan Ali","family":"Altunbas","sequence":"additional","affiliation":[{"name":"1Center for Gene and Cell Therapy, Akdeniz University, Antalya, Turkey"},{"name":"3Division of Endocrinology and Metabolic Diseases, Department of Internal Medicine, Akdeniz University Faculty of Medicine, Antalya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ercument","family":"Dirice","sequence":"additional","affiliation":[{"name":"1Center for Gene and Cell Therapy, Akdeniz University, Antalya, Turkey"},{"name":"4Department of Pharmacology, New York Medical College School of Medicine, Valhalla, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahter Dilsad","family":"Sanlioglu","sequence":"additional","affiliation":[{"name":"1Center for Gene and Cell Therapy, Akdeniz University, Antalya, Turkey"},{"name":"2Department of Medical Biology and Genetics, Akdeniz University Faculty of Medicine, Antalya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Journal of Molecular Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/jme.bioscientifica.com\/view\/journals\/jme\/66\/4\/JME-20-0037.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/jme.bioscientifica.com\/downloadpdf\/journals\/jme\/66\/4\/JME-20-0037.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:53:54Z","timestamp":1784555634000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/jme\/article\/66\/4\/325-338\/14462"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,1]]},"references-count":0,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.1530\/jme-20-0037","relation":{},"ISSN":["0952-5041","1479-6813"],"issn-type":[{"value":"0952-5041","type":"print"},{"value":"1479-6813","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,1]]}}}