PI3KAKTmetaboliareitit

PI3KAKTmetaboliareitit refers to the metabolic aspects of the PI3K–AKT signaling pathway, a cell signaling network that integrates extracellular cues with intracellular metabolic programs. The pathway is activated by signals such as insulin and growth factors and is regulated by lipid phosphatases and feedback mechanisms to coordinate growth, survival, and energy use.

Class I PI3Ks, including catalytic subunits p110α, p110β, and p110δ, are activated by receptor tyrosine kinases and G protein-coupled receptors. Activated PI3K converts PIP2 to PIP3 at the plasma membrane, creating a docking site for AKT and its activator PDK1. PTEN antagonizes the signal by dephosphorylating PIP3 back to PIP2, providing a critical brake on the pathway.

AKT activation drives multiple metabolic outcomes. It promotes glucose uptake by stimulating GLUT4 translocation to the cell surface in muscle and fat tissue, enhances glycolysis, and supports glycogen synthesis by inhibiting GSK3 and activating glycogen synthase. In the liver, AKT suppresses gluconeogenesis through inhibition of FOXO transcription factors and contributes to lipogenesis via SREBP1c.

AKT also activates mTORC1 indirectly by phosphorylating TSC2, relieving inhibition of Rheb. mTORC1 then promotes protein synthesis through S6K and 4E-BP1 and coordinates broader anabolic metabolism. The PI3K–AKT axis interacts with AMPK, hypoxia signaling, and other pathways to adapt cellular metabolism to energy and nutrient status.

Dysregulation of PI3K–AKT signaling is linked to metabolic diseases such as type 2 diabetes and obesity, and to cancer, where the axis supports growth and metabolic reprogramming. Consequently, it is a major target for therapeutic inhibitors of PI3K, AKT, and mTOR.