Preserved insulin response of Nupr1-transgenic islets during diabetogenic injury is correlated with reduced secretion of IL-1beta and enhanced secretion of IL-1 receptor antagonist

Introduction: We previously demonstrated that transgenic mice with beta cell-specific overexpression of Nupr1 (Nupr1-Tg) are resistant to multiple low-dose streptozotocin (STZ) and/or high fat diet (HFD). Preserved insulin secretion of Nupr-Tg islets in vivo was associated with reduced NF-kB activation and less lymphocyte infiltration. The pro-inflammatory cytokine IL-1beta is well known to promote beta cell apoptosis and to inhibit insulin secretion via activation of NF-kB. Therefore, we investigated the response of IL-1beta and its physiologic receptor antagonist IL-1RA in WT and Nupr1-Tg islets during diabeto…