| First Author | Wang Y | Year | 2019 |
| Journal | Diabetes | Volume | 68 |
| Issue | 10 | Pages | 1950-1964 |
| PubMed ID | 31345937 | Mgi Jnum | J:280793 |
| Mgi Id | MGI:6361833 | Doi | 10.2337/db19-0166 |
| Citation | Wang Y, et al. (2019) Dual Effect of Raptor on Neonatal beta-Cell Proliferation and Identity Maintenance. Diabetes 68(10):1950-1964 |
| abstractText | Immature pancreatic beta-cells are highly proliferative, and the expansion of beta-cells during the early neonatal period largely determines functional beta-cell mass; however, the mechanisms are poorly characterized. We generated Ngn3RapKO mice (ablation of Raptor, an essential component of mechanistic target of rapamycin [mTORC1] in Ngn3(+) endocrine progenitor cells) and found that mTORC1 was dispensable for endocrine cell lineage formation but specifically regulated both proliferation and identity maintenance of neonatal beta-cells. Ablation of Raptor in neonatal beta-cells led to autonomous loss of cell identity, decelerated cell cycle progression, compromised proliferation, and caused neonatal diabetes as a result of inadequate establishment of functional beta-cell mass at postnatal day 14. Completely different from mature beta-cells, Raptor regulated G1/S and G2/M phase cell cycle transition, thus permitting a high proliferation rate in neonatal beta-cells. Moreover, Ezh2 was identified as a critical downstream target of mTORC1 in neonatal beta-cells, which was responsible for G2/M phase transition and proliferation. Our discovery of the dual effect of mTORC1 in immature beta-cells has revealed a potential target for replenishing functional beta-cell pools by promoting both expansion and functional maturation of newly formed immature beta-cells. |
