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Figure 1: Stimulation of PI-3K/Akt signaling pathway after activation of IR/IGF-1R mediates insulin neuroprotection against damaging conditions. For example, insulin administration under oxidative stress phosphorylates IR and/or IGF-1R, which in turn activate the PI-3K/Akt signaling pathway, regulating the expression of “candidate” proteins, namely, glutathione peroxidase-1 (GPx-1), hexokinase-II (Hxk-II), and also the antiapoptotic Bcl-2 and the proapoptotic caspase-3. Thus, oxidative stress, impaired glucose metabolism and, neuronal apoptosis are counterbalanced. Insulin also interferes with GSK-3β signaling, decreasing its activated form and inhibiting apoptotic neuronal death under oxidized conditions.