biostudies-literaturePita-Grisanti VDivision of Diabetes, Endocrinology, and Metabolic DiseasesU.S. Department of Veterans Affairs316-326https://www.ebi.ac.uk/biostudies/studies/S-EPMC12823344biostudies-literatureUnknown75(2)<h4>Article highlights</h4>Mammalian target of rapamycin complex 1 (mTORC1) signaling is essential to β-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-binding protein 2 (4E-BP2), a major translational regulator downstream of mTORC1, by using global 4E-BP2-knockout mice on the NOD background. Loss of 4E-BP2 protected male NOD mice from T1D through preservation of β-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.DiabetesProtection Against Type 1 Diabetes Development in Mice With 4E-BP2 Deletion.PMC12823344R01DK133183R01DK132103T01BX002728R01DK138471Pita-Grisanti VArenas NBayer AJaramillo CBernal-Mizrachi ELouzada RABlandino-Rosano MPecanha FLMfalseProtection Against Type 1 Diabetes Development in Mice With 4E-BP2 Deletion.<h4>Article highlights</h4>Mammalian target of rapamycin complex 1 (mTORC1) signaling is essential to β-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-binding protein 2 (4E-BP2), a major translational regulator downstream of mTORC1, by using global 4E-BP2-knockout mice on the NOD background. Loss of 4E-BP2 protected male NOD mice from T1D through preservation of β-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.2026-01-01T00:00:00Z2026 Jan2026-06-06T18:08:28.434Z2026-06-04T03:10:31.174ZS-EPMC128233444123620710.2337/db25-0348