Insulin Receptor

Pathway Overview💡

The Insulin receptor is a dimer, meaning it is two identical subunits that come together.

When insulin binds, either side of the dimer phosphorylates the other.

→ Next, this complex phosphorylates the tail of IRS

→ The phosphorylation of IRS is now a binding site for phosphoinositide 3 kinase

→ This then phosphorylates PIP2 to PIP3

→ PDK1 binds to PIP3

→ PDK1 phosphorylates Akt

*More signaling* → Increase glucose transporters of GLUT4

Clinical Relevance💡

Type 2 diabetes occurs when signaling from this pathway is impaired. This results in less GLUT4 and less glucose uptake in cells

This results in hyperglycemia.

Notes

The insulin receptor is no longer a GPCR, but is now a receptor tyrosine kinase (RTK). It is a heterotetramer and contains two dimers. This means that there are 4 subunits that are paired together to create the two dimers.

The two dimers are represented to the right as two different shades of blue. One dimer is found on the left and goes up the loop and the other is on the right. They also span the membrane, exemplified by the grey rectangle.

When insulin binds, either side of the dimer phosphorylates the other. As you can see in the diagram, this is done by them moving in close proximity to eachother as the insulin causes changes.

Following this phosphorylation, the complex phosphorylates the tail of the IRS.

The next few steps are just memorization!

The phosphorylation of IRS is now a binding site for phosphoinositide 3 kinase

→ This then phosphorylates PIP2 to PIP3

→ PDK1 binds to PIP3

→ PDK1 phosphorylates Akt

More signaling that you are not responsible to know occurs to finally...

→ Increase glucose transporters of GLUT4

Note: The blue large ballon-like object in the top left corner is the inner membrane portion of the receptor.

Remember.. Since PIP3 is NOT a protein, we need to use a lipid phosphatase as well to stop signaling!

You should only need to watch this video until 2:15 (feel free to start at 0:55 to skip some unnecessary bits in the beginning if you are low on time)

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