| First Author | Böni-Schnetzler M | Year | 2018 |
| Journal | Cell Rep | Volume | 22 |
| Issue | 7 | Pages | 1774-1786 |
| PubMed ID | 29444430 | Mgi Jnum | J:271068 |
| Mgi Id | MGI:6278403 | Doi | 10.1016/j.celrep.2018.01.063 |
| Citation | Boni-Schnetzler M, et al. (2018) beta Cell-Specific Deletion of the IL-1 Receptor Antagonist Impairs beta Cell Proliferation and Insulin Secretion. Cell Rep 22(7):1774-1786 |
| abstractText | 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 beta cell (betaIL-1Ra)-specific versus myeloid-cell (myeloIL-1Ra)-specific IL-1Ra knockout (KO) mice. Deletion of IL-1Ra in beta 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. betaIL-1Ra KO mice had impaired insulin secretion, reduced beta cell proliferation, and decreased expression of islet proliferation genes, along with impaired glucose tolerance. The key cell-cycle regulator E2F1 partly reversed IL-1beta-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 beta cell-derived IL-1Ra for the local defense of beta cells to maintain normal function and proliferation. |
