| First Author | Goodyer WR | Year | 2012 |
| Journal | Dev Cell | Volume | 23 |
| Issue | 1 | Pages | 21-34 |
| PubMed ID | 22814600 | Mgi Jnum | J:187609 |
| Mgi Id | MGI:5437547 | Doi | 10.1016/j.devcel.2012.05.014 |
| Citation | Goodyer WR, et al. (2012) Neonatal beta cell development in mice and humans is regulated by calcineurin/NFAT. Dev Cell 23(1):21-34 |
| abstractText | Little is known about the mechanisms governing neonatal growth and maturation of organs. Here we demonstrate that calcineurin/Nuclear Factor of Activated T cells (Cn/NFAT) signaling regulates neonatal pancreatic development in mouse and human islets. Inactivation of calcineurin b1 (Cnb1) in mouse islets impaired dense core granule biogenesis, decreased insulin secretion, and reduced cell proliferation and mass, culminating in lethal diabetes. Pancreatic beta cells lacking Cnb1 failed to express genes revealed to be direct NFAT targets required for replication, insulin storage, and secretion. In contrast, glucokinase activation stimulated Cn-dependent expression of these genes. Calcineurin inhibitors, such as tacrolimus, used for human immunosuppression, induce diabetes. Tacrolimus exposure reduced Cn/NFAT-dependent expression of factors essential for insulin dense core granule formation and secretion and neonatal beta cell proliferation, consistent with our genetic studies. Discovery of conserved pathways regulating beta cell maturation and proliferation suggests new strategies for controlling beta cell growth or replacement in human islet diseases. |
