Role of NF-κB in β-cell death

Apoptotic beta-cell death appears to be central to the pathogenesis of Type 1 diabetes mellitus and in islet graft rejection. The beta-cell destruction is partially mediated by cytokines, such as IL-1 beta(interleukin 1 beta), TNF alpha (tumour necrosis factor alpha) and IFN-gamma (interferon gamma). IL-1 beta and TNF alpha mediate activation of the transcription factor NF kappa B (nuclear factor kappa B) pathway. Use of a degradation-resistant NF-kappa B protein inhibitor (Delta NI kappa B alpha), specifically expressed in beta-cells, significantly reduced IL-1 beta + IFN-gamma-induced apoptosis. Moreover, in vivo, it protected against multiple low-dose streptozocin-induced diabetes, with reduced intra-islet lymphocytic infiltration. Thus beta- cell-specific activation of NF kappa B is a key event in the progressive loss of beta-cells in diabetes. inhibition of this process could be a potential effective strategy for beta-cell protection.