TOSO promotes β-cell proliferation and protects from apoptosis.

Abstract

Decreased β-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 β-cell mass and normoglycemia is to improve β-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 β-cell apoptosis and increased proliferation in human islets. TOSO was clearly expressed in pancreatic β-cells and down-regulated in T2DM. TOSO expression correlated with β-cell turnover; at conditions of improved survival, TOSO was induced. In contrast, TOSO downregulation induced β-cell apoptosis. Although TOSO overexpression resulted in a 3-fold induction of proliferation, proliferating β-cells showed a very limited capacity to undergo multiple rounds of replication. Our data suggest that TOSO is an important regulator of β-cell turnover and switches β-cell apoptosis into proliferation.

DOI: 10.1016/j.molmet.2012.08.006

Cite this paper

@article{Dharmadhikari2012TOSOP, title={TOSO promotes β-cell proliferation and protects from apoptosis.}, author={G Dharmadhikari and Michael Muehle and Fabienne T. Schulthess and Svenja Laue and Jos{\'e} Oberholzer and François N. Pattou and Julie Kerr-conte and Kathrin Maedler}, journal={Molecular metabolism}, year={2012}, volume={1 1-2}, pages={70-8} }