Insulin rescues ES cell-derived neural progenitor cells from apoptosis by differential regulation of Akt and ERK pathways. 
Transplantation of embryonic stem (ES) cell-derived neural progenitor cells (ES-NPCs) is one promising technology for the treatment of spinal cord injury.  Promoting ES-NPC survival at the lesion site is critical for the successful treatment.  We tested the role of insulin in promoting mouse ES-NPC survival.  Cultured ES-NPCs survived when maintained in normoxia but underwent apoptosis when exposed to hypoxia.  Insulin rescued ES-NPCs from hypoxia-induced cell death.  This effect could be blocked by the phosphatidylinositol 3-kinase (PI3K)/Akt pathway inhibitor LY294002.  In contrast, mitogen-activated protein kinase (MAP)/extracellular-signal-regulated kinase (ERK) pathway inhibitor U0126 potentiated insulin-mediated survival.  Immunoblots revealed that insulin upregulated activation of Akt and inhibited ERK activation through the PI3K pathway.  In addition, we showed that insulin reduced the activation of caspase-3, the key executor of apoptosis.  In summary, our data suggest that insulin prevent apoptosis in ES-NPCs by activating Akt and inhibiting ERK through the PI3K pathway.