Fig. 2.

Insulin signaling pathway. Binding of insulin to the extracellular (α) domain leads to phosphorylation of IRS by the β domain, which in turn activates PI3K leading to conversion of PIP2 to PIP3. PIP3 activates PDK1. AKT is activated by the combined actions of PDK1 and mTORC2. AKT activation results in metabolic actions of insulin. DAG and ceramide inhibits insulin signaling by inhibiting IRS and AKT, respectively. DAG: Diacylglycerol; IRS: insulin receptor substrate; mTORC2: mammalian target of rapamycin complex 2; PDK1: phosphoinositide dependent protein kinase 1; PI3K: phosphoinositide 3-kinase; PIP2: phosphatidylinositol bisphosphate; PIP3: phosphatidylinositol triphosphate