Sub-clinical inflammation is a recently discovered phenomenon in type 2 diabetes (T2DM). Elevated cytokines impair -cell function and survival. A recent clinical trial shows that blocking Interleukin-1 (IL-1) signaling by Interleukin-1 Receptor Antagonist (IL-1Ra) improves -cell secretory function in patients with T2DM. In the present study we provide further mechanisms of the protective role of IL-1Ra on the -cell.

IL-1Ra prevented diabetes in vivo in C57BL/6J mice fed a high fat/ high sucrose diet (HFD) for 12 weeks, it improved glucose tolerance and insulin secretion. High fat diet treatment increased serum levels of free fatty acids and of the adipokines resistin and leptin, which was reduced by IL-1Ra treatment. In addition, IL-1Ra counteracted adiponectin levels, which were decreased by high fat feeding.

Studies on isolated islets revealed that IL-1Ra specifically acted on the -cell. IL-1Ra protected islets from HFD treated animals from -cell apoptosis, induced -cell proliferation and improved glucose-stimulated insulin secretion. Insulin mRNA was reduced in islets from mice fed a HFD, but normalized in the IL-1Ra group. Our results show that IL-1Ra improves -cell survival and function and support the potential role for IL-1Ra in the treatment of diabetes.