| First Author | Cai Z | Year | 2022 |
| Journal | J Genet Genomics | Volume | 49 |
| Issue | 3 | Pages | 208-216 |
| PubMed ID | 34861413 | Mgi Jnum | J:360217 |
| Mgi Id | MGI:7797535 | Doi | 10.1016/j.jgg.2021.11.006 |
| Citation | Cai Z, et al. (2022) GRB10 regulates beta-cell mass by inhibiting beta-cell proliferation and stimulating beta-cell dedifferentiation. J Genet Genomics 49(3):208-216 |
| abstractText | Decreased functional beta-cell mass is the hallmark of diabetes, but the cause of this metabolic defect remains elusive. Here, we show that the levels of the growth factor receptor-bound protein 10 (GRB10), a negative regulator of insulin and mTORC1 signaling, are markedly induced in islets of diabetic mice and high glucose-treated insulinoma cell line INS-1 cells. beta-cell-specific knockout of Grb10 in mice increased beta-cell mass and improved beta-cell function. Grb10-deficient beta-cells exhibit enhanced mTORC1 signaling and reduced beta-cell dedifferentiation, which could be blocked by rapamycin. On the contrary, Grb10 overexpression induced beta-cell dedifferentiation in MIN6 cells. Our study identifies GRB10 as a critical regulator of beta-cell dedifferentiation and beta-cell mass, which exerts its effect by inhibiting mTORC1 signaling. |
