PhysiologyTier 1Medical Sciences concept

Insulin receptor signalling mechanism (tyrosine kinase)

Core concept

  • Insulin receptor = receptor tyrosine kinase, constitutive heterotetramer (alpha2-beta2), disulphide-linked
    • Alpha subunits extracellular = ligand binding, tonically inhibit the kinase
    • Beta subunits transmembrane = intrinsic tyrosine kinase
    • No dimerisation step needed - insulin relieves autoinhibition rather than bringing monomers together
  • Cascade
    • Insulin binds alpha
    • beta-subunit trans-autophosphorylation on tyrosine
    • phosphorylates IRS-1/IRS-2 on tyrosine
    • -> two limbs
      • PI3K -> PIP3 -> PDK1 -> Akt/PKB = the metabolic limb
      • Grb2/SOS -> Ras -> Raf -> MEK -> MAPK = the mitogenic/growth limb
  • Akt is the metabolic effector
    • AS160 phosphorylated -> GLUT4 vesicles translocate to the membrane (muscle, adipose)
    • GSK-3 inhibited -> glycogen synthase active -> glycogenesis
    • FOXO1 excluded from nucleus -> dec PEPCK/G6Pase -> dec gluconeogenesis
    • mTORC1 activated -> protein synthesis; SREBP-1c -> lipogenesis
    • Phosphodiesterase-3B -> dec cAMP -> dec hormone-sensitive lipase -> dec lipolysis

3 more sections, plus exam facts

Premium unlocks every note across every specialty, and the full exam fact library behind it.

Get premium access