Fructose supplementation induces hyperinsulinemia and insulin resistance in animal models, shown by the inhibition of different steps in the insulin signaling pathway: reduced tyrosine phosphorylation of the insulin receptor and of insulin receptor substrates (IRS), reduced association of IRS with PI3K and/or inhibition of PI3K activity and Akt phosphorylation [80]. The gene discussed is INSR; the disease is Hyperinsulinemia.