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Proposed model summarizing the findings of this study. Under normal conditions, both insulin and IGF-I reduce APP phosphorylation through an Akt-mediated pathway. In IR, the PI3-K/Akt pathway is compromised, leading to an almost complete inhibition of the insulin-mediated reduction in APP phosphorylation. IGF-I still is able to reduce APP phosphorylation under IR conditions, but its effect is greatly reduced.
