Abstract：
: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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Böni-Schnetzler M,Häuselmann SP,Dalmas E,Meier DT,Thienel C,Traub S,Schulze F,Steiger L,Dror E,Martin P,Herrera PL,Gabay C,Donath MYdoi
10.1016/j.celrep.2018.01.063subject
Has Abstractpub_date
2018-02-13 00:00:00pages
1774-1786issue
7issn
2211-1247pii
S2211-1247(18)30112-8journal_volume
22pub_type
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