| Autor: |
Yael Riahi, Tal Israeli, Roni Yeroslaviz, Shoshana Chimenez, Dana Avrahami, Miri Stolovich-Rain, Ido Alter, Marina Sebag, Nava Polin, Ernesto Bernal-Mizrachi, Yuval Dor, Erol Cerasi, Gil Leibowitz |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
|
| Zdroj: |
eLife, Vol 7 (2018) |
| Druh dokumentu: |
article |
| ISSN: |
2050-084X |
| DOI: |
10.7554/eLife.38472 |
| Popis: |
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 β-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 β-cell apoptosis throughout life. Surprisingly, we found that the main mechanism leading to β-cell dysfunction is marked impairment of β-cell growth during the early postnatal life due to transient inhibition of mTORC1, which governs postnatal β-cell growth and differentiation. Importantly, restoration of mTORC1 activity in neonate β-cells was sufficient to rescue postnatal β-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 β-cell mass expansion due to mTOR inhibition. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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