Fig. 1

Coordinated regulation of exogenous glucose uptake from circulation and endogenous glucose production through gluconeogenesis and glycogenolysis. Insulin receptors stimulate phosphorylation/activation of IRS and subsequently activation of PI3K cascade which is the main pathway involved in glucose transport. PI3K stimulates phosphorylation of AKT and GSK3, which increases and decreases their activities respectively. The function of the previously mentioned kinases of PI3K/AKT pathway is antagonized by PTEN phosphatase. AKT phosphorylates/inactivates GSK3 and increases glycogen synthase activity. Also, AKT inhibits FOX01 which results in inhibition of gluconeogenesis by suppressing G6pc and Pck1. PI3K via PDK1 activates PKC that stimulates gluconeogenesis and contributes to insulin resistance by converting free fatty acids to Acetyl-CoA, which activates pyruvate carboxylase