Furthermore, insulin signaling to IRS-1/PI3K, Akt and aPKC in muscle is secondarily downregulated, most likely through release of inhibitory lipids and proinflammatory substances, e.g., nuclear factor kappa-B(NFκB)-dependent tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) [1,10,12,13,17] from the liver; as a result, muscle glucose transport is diminished, and glucose intolerance worsens. The gene discussed is AKT1; the disease is Glucose intolerance.