4.7 Article

IL-1beta promotes the age-associated decline of beta cell function

Journal

ISCIENCE
Volume 24, Issue 11, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.isci.2021.103250

Keywords

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Funding

  1. Swiss National Science Foundation, Switzerland

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The study found that the expression level of IL-1β can affect insulin secretion as age increases, while specific knockout of IL-1β may help preserve insulin secretion levels and enhance islet function.
Aging is the prime risk factor for the development of type 2 diabetes. We investigated the role of the interleukin-1 (IL-1) system on insulin secretion in aged mice. During aging, expression of the protective IL-1 receptor antagonist decreased in islets, whereas IL- 1beta gene expression increased specifically in the CD45 + islet immune cell fraction. One-year- old mice with a whole-body knockout of IL-1beta had higher insulin secretion in vivo and in isolated islets, along with enhanced proliferation marker Ki67 and elevated size and number of islets. Myeloid cell-specific IL-1beta knockout preserved glucose- stimulated insulin secretion during aging, whereas it declined in control mice. Isolated islets from aged myeloIL-1beta ko mice secreted more insulin along with increased expression of Ins2, Kir6.2, and of the cell-cycle gene E2f1. IL-1beta treatment of isolated islets reduced E2f1, Ins2, and Kir6.2 expression in beta cells. We conclude that IL-1beta contributes the age-associated decline of beta cell function.

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