| Autor: |
Marianne Böni-Schnetzler, Stéphanie P. Häuselmann, Elise Dalmas, Daniel T. Meier, Constanze Thienel, Shuyang Traub, Friederike Schulze, Laura Steiger, Erez Dror, Praxedis Martin, Pedro L. Herrera, Cem Gabay, Marc Y. Donath |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 22, Iss 7, Pp 1774-1786 (2018) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2018.01.063 |
| Popis: |
Summary: Interleukin-1 receptor antagonist (IL-1Ra) is elevated in the circulation during obesity and type 2 diabetes (T2D) but is decreased in islets from patients with T2D. The protective role of local IL-1Ra was investigated in pancreatic islet β cell (βIL-1Ra)-specific versus myeloid-cell (myeloIL-1Ra)-specific IL-1Ra knockout (KO) mice. Deletion of IL-1Ra in β cells, but not in myeloid cells, resulted in diminished islet IL-1Ra expression. Myeloid cells were not the main source of circulating IL-1Ra in obesity. βIL-1Ra KO mice had impaired insulin secretion, reduced β cell proliferation, and decreased expression of islet proliferation genes, along with impaired glucose tolerance. The key cell-cycle regulator E2F1 partly reversed IL-1β-mediated inhibition of potassium channel Kir6.2 expression and rescued impaired insulin secretion in IL-1Ra knockout islets. Our findings provide evidence for the importance of β cell-derived IL-1Ra for the local defense of β cells to maintain normal function and proliferation. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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