In the liver and adipose tissue activated PP2A dephosphorylates stimulatory pT308 of Akt.352–355 In addition, hepatic and adipocyte exposure to ceramides stimulates PKC isoform Zeta (PKC-ξ), leading to the inhibitory phosphorylation of Akt at T34.356,357 The inhibition of the central kinase behind the insulin signaling cascade Akt results in impaired glucose tolerance and insulin resistance, the key phenotype of T2DM. The gene discussed is AKT1; the disease is type 2 diabetes mellitus.