AKT pathway

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When glucose levels increase, insulin is produced and delivered to target tissues where it binds to its receptor, insulin receptor (IR) and activates the AKT pathway.

Insulin binding to its receptor promotes IRS1 (insulin receptor substrate 1) autophosphorilation. Phosphorylated IRS1 activates PI3K that phosphorylates phospahitidylinositol-bisphosphate (PI2P) to produce phosphatidylinositol-tryphosphate (PI3P)

PI3P activates PDK1, a protein kynase that phosphorulate and, consequently, activates AKT.

Activated AKT promotes translocation of the glucose transporter GLUT4 to the membrane to increase glucose uptake.

AKT inhibits GSK3, an inhibitor og glycogen syntesis. Then, AKT activates glycogen synthesis to increase glucose storage.

AKT inhibits FOXO, a family of transcription factors that promotes glucose synthesis. Then, AKT inhibits glucose synthesis.

AKT activates mTORC1 by separating TSC1/TSC2 complex, which inhibits mTORC1

The activation of mTORC1 triggers different pathways to control energetic and aminoacid metabolism. Among the factors activated by mTORC1 is p70 that inhibits AKT pathway by inhibiting IRS1 autophosphorylation. Then, this is the hegative feedback loop of this pathway

Another mTORC complex, mTORC2 also activates AKT phosphorylation.