The IGF1R-IR/PI3K/Akt/mTOR pathway and its manipulation through diet. Elevations in blood glucose concentrations lead to secretion of insulin with subsequent elevation of free IGF1. Binding of insulin and IGF1 to their receptor tyrosine kinases induces autophosphorylation of the latter which leads to subsequent activation of PI3K by one of at least three different pathways . Further downstream, PI3K signaling causes phosphorylation and activation of the serine/threonine kinase Akt (also known as protein kinase B). Akt activates mammalian target of rapamycin (mTOR), which itself induces aerobic glycolysis by up-regulating key glycolytic enzymes, in particular via its downstream effectors c-Myc and hypoxia inducible factor (HIF)-1α. mTOR is negatively affected through activation of AMPK, which can be achieved by dietary restriction . In addition, a possible negative interaction between insulin and AMPK is discussed in vivo .
Klement and Kämmerer Nutrition & Metabolism 2011 8:75 doi:10.1186/1743-7075-8-75