| First Author | Riahi Y | Year | 2018 |
| Journal | Elife | Volume | 7 |
| PubMed ID | 30412050 | Mgi Jnum | J:272206 |
| Mgi Id | MGI:6281252 | Doi | 10.7554/eLife.38472 |
| Citation | Riahi Y, et al. (2018) Inhibition of mTORC1 by ER stress impairs neonatal beta-cell expansion and predisposes to diabetes in the Akita mouse. Elife 7:e38472 |
| abstractText | Unresolved ER stress followed by cell death is recognized as the main cause of a multitude of pathologies including neonatal diabetes. A systematic analysis of the mechanisms of beta-cell loss and dysfunction in Akita mice, in which a mutation in the proinsulin gene causes a severe form of permanent neonatal diabetes, showed no increase in beta-cell apoptosis throughout life. Surprisingly, we found that the main mechanism leading to beta-cell dysfunction is marked impairment of beta-cell growth during the early postnatal life due to transient inhibition of mTORC1, which governs postnatal beta-cell growth and differentiation. Importantly, restoration of mTORC1 activity in neonate beta-cells was sufficient to rescue postnatal beta-cell growth, and to improve diabetes. We propose a scenario for the development of permanent neonatal diabetes, possibly also common forms of diabetes, where early-life events inducing ER stress affect beta-cell mass expansion due to mTOR inhibition. |
