Send to

Choose Destination
Cell Death Dis. 2014 Oct 23;5:e1487. doi: 10.1038/cddis.2014.441.

Pro-oxidant/antioxidant balance controls pancreatic β-cell differentiation through the ERK1/2 pathway.

Author information

1] INSERM, U1016, Institut Cochin, Paris, France [2] Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France.
INSERM U676, Hopital Robert Debre, Paris, France.


During embryogenesis, the intrauterine milieu affects cell proliferation, differentiation, and function by modifying gene expression in susceptible cells, such as the pancreatic β-cells. In this limited energy environment, mitochondrial dysfunction can lead to overproduction of reactive oxygen species (ROS) and to a decline in β-cell function. In opposition to this toxicity, ROS are also required for insulin secretion. Here we investigated the role of ROS in β-cell development. Surprisingly, decreasing ROS production in vivo reduced β-cell differentiation. Moreover, in cultures of pancreatic explants, progenitors were highly sensitive to ROS stimulation and responded by generating β-cells. ROS enhanced β-cell differentiation through modulation of ERK1/2 signaling. Gene transfer and pharmacological manipulations, which diminish cellular ROS levels, also interfered with normal β-cell differentiation. This study highlights the role of the redox balance on β-cell development and provides information that will be useful for improving β-cell production from embryonic stem cells, a step in cell therapy for diabetes.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center