Protection Against Type 1 Diabetes Development in Mice With 4E-BP2 Deletion
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.
Authors
- Ernesto Bernal‐Mizrachi (ORCID: https://orcid.org/0000-0001-9997-3301)
- Valentina Pita-Grisanti (ORCID: https://orcid.org/0000-0002-0291-2017)
- Ruy A. N. Louzada (ORCID: https://orcid.org/0000-0003-1789-4234)
- Flavia Letícia Martins Peçanha (ORCID: https://orcid.org/0000-0001-9588-8468)
- Allison L. Bayer (ORCID: https://orcid.org/0000-0003-4778-0238)
- Manuel Blandino-Rosano (ORCID: https://orcid.org/0000-0002-1712-8233)
- Camillo Jaramillo
- Natalia Arenas
Institutions
- University of Miami (US)
- Veterans Health Administration (US)
- University of Florida (US)
- Geriatric Research Education and Clinical Center (US)
- South Florida Veterans Affairs Foundation for Research and Education (US)
- Florida College (US)
Publication Details
- Journal
- Diabetes
- Published
- 2025-11-14
- DOI
- https://doi.org/10.2337/db25-0348
- Primary Topic
- Diabetes and associated disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- University of Miami
- Leonard M. Miller School of Medicine