摘要：SummaryAging 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 secretionin vivoand 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 ofIns2,Kir6.2, and of the cell-cycle geneE2f1. IL-1beta treatment of isolated islets reducedE2f1,Ins2, andKir6.2expression in beta cells. We conclude that IL-1beta contributes the age-associated decline of beta cell function.Graphical abstractDisplay OmittedHighlights•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 agingCell biology; Cellular physiology; Physiology
