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Mediators and mechanisms of pancreatic beta-cell death in type 1 diabetes

2008; Editora da Universidade de São Paulo; Volume: 52; Issue: 2 Linguagem: Inglês

10.1590/s0004-27302008000200003

1677-9487

Pierre Pirot, Alessandra K. Cardozo, Décio L. Eizirik,

Diet, Metabolism, and Disease

Type 1 diabetes mellitus (T1D) is characterized by severe insulin deficiency resulting from chronic and progressive destruction of pancreatic beta-cells by the immune system. The triggering of autoimmunity against the beta-cells is probably caused by environmental agent(s) acting in the context of a predisposing genetic background. Once activated, the immune cells invade the islets and mediate their deleterious effects on beta-cells via mechanisms such as Fas/FasL, perforin/granzyme, reactive oxygen and nitrogen species and pro-inflammatory cytokines. Binding of cytokines to their receptors on the beta-cells activates MAP-kinases and the transcription factors STAT-1 and NFkappa-B, provoking functional impairment, endoplasmic reticulum stress and ultimately apoptosis. This review discusses the potential mediators and mechanisms leading to beta-cell destruction in T1D.