Membrane-near intracellular diacyglycerols lead to activation of PKC-ε which, in turn, inhibits the insulin receptor kinase. This then leads to decreased insulin-stimulated tyrosine phosphorylation (pY) of insulin receptor substrate-1 and -2 (IRS-1, IRS-2), PI3K activation and downstream insulin signaling. The net result is a decreased in hepatic glycogen synthesis, owing to decreased activation of glycogen synthase, and increased hepatic gluconeogenesis through reduced inactivation of FOXO1, which results in an exaggerated glucose release through glucose transporter 2 (GLUT2).