The Role of Insulin and Insulin-Like Growth Factor-1/FoxO-Mediated Transcription for the Pathogenesis of Obesity-Associated Dementia
Figure 1
Central IR/IGF-1 signaling. Binding of insulin and IGF-1 to their receptors leads to autophosphorylation of the β-subunits of the IR or IGF-1R, recruitment of IRS-1/-2, and subsequently activation of mainly two pathways the PI3 kinase pathway and the MAP kinase cascade. The PI3 kinase pathway activates Akt which inhibits GSK-3β. Akt-mediated FoxO1 phosphorylation results in binding of the regulatory protein 14-3-3 and nuclear exclusion of FoxO1. Abbreviations: IR, insulin receptor; IGF-1R, insulin-like growth factor-1 receptor; IRS, insulin receptor substrate; PI3K, PI3 kinase; FoxO1, forkhead-box protein O1; PDK, phosphatidylinositide-dependent kinase; p110/p85, catalytic/regulatory subunit of PI3K; PI3,4P, phosphatidylinositide 3,4-diphosphate; PI3,4,5P, phosphatidylinositide 3,4,5-triphosphate; PTEN, phosphatase and tensin homolog deleted on chromosome ten; 14-3-3, regulatory protein 14-3-3; PP2A, protein phosphatase 2A.
