Figure 1: Illustration of the antagonist association between the insulin and AMPK pathways, two main energy metabolic systems of body
LKB1/AMPK/TSC/mTORC1 pathway is the fundamental nutrient and metabolic status sensing in the body that help cells to adjust their metabolism to the intracellular energy status and extracellular environment. The anabolic insulin pathway and catabolic AMPK (in the skeletal muscle) pathways have a negative regulatory effect on each other and both determine the level of the energy status of the cell. AMPK pathway is activated following lower energy status, which increases the level of AMP/ATP ratio in the body. Increase of the level of adiponectin following coloric restriction has a stimulatory effect on the stimulation of AMPK. AMPK decreases inflammation by enhancing fatty acid oxidation in cell. It also has a stimulatory effect on autophagy and TSC, which inhibits insulin pathway. RheB in insulin pathway via positive influence on mTOR/Rictor (TORC1) influences on the central energy sensor of the cell. TORC1 inhibits autophagy and stimulates cell growth and survival. IR: Insuli receptor, IRS: Insulin receptor substrate, AMPK: Adenosine monophosphate-activated protein kinase, PI3K: Phosphatidylinositol 3 kinase, PDK: Phosphoinositide dependent kinases, Akt/PKB: Protein kinase B, RheB: Ras homolog enriched in brain, P70S6K: P70 ribosomal S6 kinase, GLUT4: Glucose transporter type 4, EBP1: ErbB-3 binding protein, eLF-4E: Eukaryotic initiation factors-4E, ULK1: unc-51-like kinase 1, ATG13: Authophagy gene, AD: Adiponectin, AICAR: 5 aminoimidazole 4 carboxamide 1 dribofuranoside.