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

ABSTRACT: Summary 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. Graphical abstract Highlights • Islets from aged mice have increased IL-1beta and decreased IL-1Ra expression• Islet immune cells are the source of increased IL-1beta expression during aging• Myeloid-cell-specific IL-1beta knockout preserves insulin secretion in aged mice• IL-1beta targets genes regulating insulin secretion and proliferation during aging Cell biology; Cellular physiology; Physiology

SUBMITTER: Boni-Schnetzler M

PROVIDER: S-EPMC8554531 | biostudies-literature |

REPOSITORIES: biostudies-literature

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