TOSO promotes -cell proliferation and protects from apoptosis

摘要

Decreased @b-cell mass reflects a shift from quiescence/proliferation into apoptosis, it plays a crucial role in the pathophysiology of diabetes. A major attempt to restore @b-cell mass and normoglycemia is to improve @b-cell survival. Here we show that switching off the Fas pathway using Fas apoptotic inhibitory protein (Faim/TOSO), which regulates apoptosis upstream of caspase 8, blocked @b-cell apoptosis and increased proliferation in human islets. TOSO was clearly expressed in pancreatic @b-cells and down-regulated in T2DM. TOSO expression correlated with @b-cell turnover; at conditions of improved survival, TOSO was induced. In contrast, TOSO downregulation induced @b-cell apoptosis. Although TOSO overexpression resulted in a 3-fold induction of proliferation, proliferating @b-cells showed a very limited capacity to undergo multiple rounds of replication. Our data suggest that TOSO is an important regulator of @b-cell turnover and switches @b-cell apoptosis into proliferation.