Expansion
A receptor tyrosine kinase acting through IRS and PI3K to recruit GLUT4
Expansion
- Insulin binds its receptor tyrosine kinase, a tetramer of two alpha and two beta subunits
- Autophosphorylation of the beta subunits
- Phosphorylation of insulin receptor substrate (IRS) proteins
- Two arms:
- PI3K/Akt: the metabolic arm. Translocates GLUT4 to the membrane, activates glycogen synthase, inhibits gluconeogenesis and lipolysis
- MAP kinase: the growth arm, driving proliferation
GLUT transporters are worth separating:
| Transporter | Site | Notes |
|---|---|---|
| GLUT1 | Red cells, brain, placenta | Basal uptake |
| GLUT2 | Liver, pancreatic beta cell, kidney, gut | High Km, so it senses glucose |
| GLUT3 | Neurones | Low Km, high affinity |
| GLUT4 | Muscle and adipose | Insulin dependent |
Insulin resistance in type 2 diabetes acts principally at the post-receptor level, with impaired IRS signalling, which is why receptor numbers are usually normal. Notably, the growth arm often remains sensitive while the metabolic arm is resistant, which is thought to contribute to the vascular consequences of hyperinsulinaemia.