Fig. 2.

Interrelationships between growth factor, nutrient availability and energy sensing pathways in metabolic regulation in health. The Ras/ERK and PI3K/Akt pathways are activated upon insulin/IGF1 stimulation. Akt, a key effector of insulin/PI3K signalling mediates most of the metabolic actions of insulin, notably stimulation of glucose uptake and glycogen synthesis and inhibition of lipolysis. The mTOR pathway integrates signals from growth factor stimulation (via Akt), aminoacid availability and energy status (via AMPK). mTOR-activated S6K1 is a key component of a feedback loop that downregulates insulin's signal. FOXO transcription factors, which upon phosphorylation by Akt are inhibited through nuclear exclusion, also have metabolic roles, prominently in the regulation of gluconeogenesis. AMPK is activated by low energy (high AMP/ATP and/or ADP/ATP ratio) stress via phosphorylation by LKB1 and promotes glucose uptake and fatty acid oxidation. The majority of the molecular components of these pathways have been omitted from the schematic for simplicity