Figure 2: The interactions of intracellular signaling pathways implicated in diabetes and neurodegeneration. Insulin signaling initiates a series of protective intracellular signaling cascades that regulate systemic metabolic state, protect cells from apoptosis and reduce inflammation. In diabetes and neurodegenerative disease, reduced insulin signaling reduces activation of Akt and mTOR resulting in cell-destructive fate. Light grey shaded factors are generally regarded as neuroprotective or beneficial to maintaining cellular health and are upregulated in response to insulin signaling. Black-shaded factors are generally regarded as destructive and normally kept at low expression by normal insulin signaling. IGF = insulin-like growth factor; IRS = insulin receptor substrate; GLUT4 = glucose transporter 4; PI3K = phosphoinositide-3 kinase; PDK1 = phosphoinositidedependent kinase; Akt = protein kinase B; p70S6K = ribosomal protein S6 kinase; Mtor = mammalian target of rapamycin; GSK3β = glucagon synthase kinase 3 beta; PPARβ = peroxisome proliferator-activated receptor gamma; TZD = Thiozolidinedione; FOXO = Forkhead box ‘O’ type.