| First Author | Alejandro EU | Year | 2015 |
| Journal | Cell Rep | Volume | 13 |
| Issue | 11 | Pages | 2527-2538 |
| PubMed ID | 26673325 | Mgi Jnum | J:269853 |
| Mgi Id | MGI:6274070 | Doi | 10.1016/j.celrep.2015.11.020 |
| Citation | Alejandro EU, et al. (2015) Disruption of O-linked N-Acetylglucosamine Signaling Induces ER Stress and beta Cell Failure. Cell Rep 13(11):2527-2538 |
| abstractText | Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. However, the requirement of O-GlcNAcylation for maintaining glucose homeostasis by regulating pancreatic beta cell mass and function is unclear. Here, we reveal that mice lacking beta cell OGT (betaOGT-KO) develop diabetes and beta cell failure. betaOGT-KO mice demonstrated increased ER stress and distended ER architecture, and these changes ultimately caused the loss of beta cell mass due to ER-stress-induced apoptosis and decreased proliferation. Akt1/2 signaling was also dampened in betaOGT-KO islets. The mechanistic role of these processes was demonstrated by rescuing the phenotype of betaOGT-KO mice with concomitant Chop gene deletion or genetic reconstitution of Akt2. These findings identify OGT as a regulator of beta cell mass and function and provide a direct link between O-GlcNAcylation and beta cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling. |
