AKT1 and diabetes mellitus: A rare missense mutation (R274H) in AKT2 found in diabetes patients results in the loss of kinase activity.469 Although other missense mutations (such as R208K and R467W) do not cause a loss of kinase activity in vitro,470 functional loss mutations in AKT can impede the normal activation of its downstream targets, mTORC1 and GSK-3β, leading to reduced glycogen synthesis and impaired glucose uptake.471 Furthermore, dysregulation of AKT signaling is associated with increased lipolysis in adipocytes, which exacerbates insulin resistance and hyperglycemia.472