{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:03:57Z","timestamp":1781715837376,"version":"3.54.5"},"reference-count":34,"publisher":"American Diabetes Association","issue":"2","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["R01DK132103"],"award-info":[{"award-number":["R01DK132103"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["R01DK133183"],"award-info":[{"award-number":["R01DK133183"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["R01DK138471"],"award-info":[{"award-number":["R01DK138471"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["T01BX002728"],"award-info":[{"award-number":["T01BX002728"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,2,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Type 1 diabetes (T1D) is an autoimmune disease characterized by \u03b2-cell destruction promoted by autoreactive T cells. Eukaryotic translation initiation factor 4E (eIF4E)\u2013binding protein 1 (4E-BP1) and 4E-BP2 are translational repressors and downstream targets of mammalian target of rapamycin complex 1 (mTORC1). Activation of the 4E-BP2\/eIF4E pathway by 4E-BP2 deletion promotes translation initiation, inducing \u03b2-cell expansion and proliferation and regulating adaptive immunity. However, the involvement of 4E-BP2 in T1D remains unexplored. This study aimed to determine the role of 4E-BP2\/eIF4E signaling in T1D prevention. We used the NOD mouse model of T1D and generated mice with global 4E-BP2 deletion in the NOD background (Eif4ebp2\u2212\/\u2212). We assessed T1D development, glucose homeostasis, pancreas morphometry, and immune responses in Eif4ebp2\u2212\/\u2212 and littermate control mice. We found that Eif4ebp2\u2212\/\u2212 male mice exhibited reduced diabetes incidence, which did not occur in female mice, as well as preserved \u03b2-cell mass, improved insulin secretion in\u00a0vitro, and comparable insulitis. Characterization of T-cell compartments showed decreased splenic CD8+ cytotoxic T-cell proliferation and increased pancreatic regulatory T-cell infiltration in Eif4ebp2\u2212\/\u2212 mice, potentially resulting from increased proliferation and suppressive capacity. Adoptive transfer studies demonstrated that Eif4ebp2\u2212\/\u2212 male lymphocytes were less diabetogenic than those of controls. In conclusion, activation of 4E-BP2\/eIF4E by 4E-BP2 deletion protected against T1D, supporting 4E-BP2 as a potential therapy target.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>Mammalian target of rapamycin complex 1 (mTORC1) signaling is essential to \u03b2-cell mass, function, and adaptive immunity; however, its specific downstream mediators in type 1 diabetes (T1D) remain poorly defined. We investigated eukaryotic translation initiation factor 4E\u2013binding protein 2 (4E-BP2), a major translational regulator downstream of mTORC1, by using global 4E-BP2\u2013knockout mice on the NOD background. Loss of 4E-BP2 protected male NOD mice from T1D through preservation of \u03b2-cell mass and function, coupled with attenuation of autoimmune responses. These findings identify 4E-BP2 as a novel immunometabolic node, highlighting its potential as a therapeutic target for T1D prevention and treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-0348","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T14:32:22Z","timestamp":1763130742000},"page":"316-326","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["Protection Against Type 1 Diabetes Development in Mice With 4E-BP2 Deletion"],"prefix":"10.2337","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0291-2017","authenticated-orcid":false,"given":"Valentina","family":"Pita-Grisanti","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Miami Miller School of Medicine 1 , Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia Leticia Martins","family":"Pe\u00e7anha","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Miami Miller School of Medicine 1 , Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruy A.","family":"Louzada","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Miami Miller School of Medicine 1 , Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Blandino-Rosano","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Miami Miller School of Medicine 1 , Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camillo","family":"Jaramillo","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Miami Miller School of Medicine 1 , Miami, FL"},{"name":"Department of Microbiology and Immunology, University of Miami Miller School of Medicine 2 , Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Arenas","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Miami Miller School of Medicine 2 , Miami, FL"},{"name":"Department of Pathology, Immunology and Laboratory Medicine and Diabetes Institute, University of Florida College of Medicine 3 , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4778-0238","authenticated-orcid":false,"given":"Allison","family":"Bayer","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Miami Miller School of Medicine 1 , Miami, FL"},{"name":"Department of Microbiology and Immunology, University of Miami Miller School of Medicine 2 , Miami, FL"},{"name":"Department of Pathology, Immunology and Laboratory Medicine and Diabetes Institute, University of Florida College of Medicine 3 , Gainesville, FL"},{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine 5 , Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9997-3301","authenticated-orcid":false,"given":"Ernesto","family":"Bernal-Mizrachi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Miami Miller School of Medicine 1 , Miami, FL"},{"name":"Geriatric Research, Education, and Clinical Center and Research Service, Veterans Affairs Medical Center 4 , Miami, FL"},{"name":"Diabetes Research Institute, University of Miami Miller School of Medicine 5 , Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2025,11,14]]},"reference":[{"key":"2026061712173338200_B1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nri3422","article-title":"Type 1 diabetes: translating mechanistic observations into effective clinical outcomes","volume":"13","author":"Herold","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"2026061712173338200_B2","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.cmet.2018.11.014","article-title":"A map of human type 1 diabetes progression by imaging mass cytometry","volume":"29","author":"Damond","year":"2019","journal-title":"Cell Metab"},{"key":"2026061712173338200_B3","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1084\/jem.20040139","article-title":"In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes","volume":"199","author":"Tang","year":"2004","journal-title":"J Exp 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