Editorial Volume 5, Issue 8 pp 582—583

Figure 1. In normal insulin action (left panel), insulin binds and activates the insulin receptor kinase leading to phosphorylation of IRS proteins, recruitment and activation of PI3K, activation of Akt and ultimately suppression of glucose production and stimulation of glucose uptake and storage as glycogen. Recent studies, have indicated that in hepatic insulin resistance this signaling mechanism is defective (right panel). Hepatic accumulation of diacylglycerols (DAGs) due to: 1) increased delivery of fatty acids to the liver, 2) increased de novo lipogenesis and/or 3) decreased hepatic fat oxidation triggers PKCε activation which in turn inhibits insulin receptor kinase activity leading to disruption of downstream insulin signaling, thus resulting in an inadequate ability of insulin to suppress hepatic glucose production and glucose uptake and storage as glycogen.