| First Author | Yin Q | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 2538 |
| PubMed ID | 32439909 | Mgi Jnum | J:292255 |
| Mgi Id | MGI:6447684 | Doi | 10.1038/s41467-020-15935-0 |
| Citation | Yin Q, et al. (2020) Raptor determines beta-cell identity and plasticity independent of hyperglycemia in mice. Nat Commun 11(1):2538 |
| abstractText | Compromised beta-cell identity is emerging as an important contributor to beta-cell failure in diabetes; however, the precise mechanism independent of hyperglycemia is under investigation. We have previously reported that mTORC1/Raptor regulates functional maturation in beta-cells. In the present study, we find that diabetic beta-cell specific Raptor-deficient mice (betaRapKO(GFP)) show reduced beta-cell mass, loss of beta-cell identity and acquisition of alpha-cell features; which are not reversible upon glucose normalization. Deletion of Raptor directly impairs beta-cell identity, mitochondrial metabolic coupling and protein synthetic activity, leading to beta-cell failure. Moreover, loss of Raptor activates alpha-cell transcription factor MafB (via modulating C/EBPbeta isoform ratio) and several alpha-cell enriched genes i.e. Etv1 and Tspan12, thus initiates beta- to alpha-cell reprograming. The present findings highlight mTORC1 as a metabolic rheostat for stabilizing beta-cell identity and repressing alpha-cell program at normoglycemic level, which might present therapeutic opportunities for treatment of diabetes. |
