Insulin signalling

Question 1

Which clinical conditions arise from mutations in the insulin receptor?

Answer 1

1. Leprechaunism
2. Rabson-Mendenhall syndrome
3. Type A insulin resistance

Question 2

What does insulin binding to its receptor result in?

Answer 2

Autophosphorylation of the receptor

Question 3

What does insulin binding activate?

Answer 3

IRS- insulin receptor substrate

Question 4

What does IRS contain?

Answer 4

Phosphotyrosine binding domain- highly phosphorylated by the insulin receptor

Question 5

Where is PKB recruited?

Answer 5

Protein kinase B is recruited to the membrane after PI3 phosphorylates its targets
Creates a docking site for PKB
PKB is phosphorylated by membrane associated kinases such as PKD1

Question 6

What finally happens to PKB?

Answer 6

PKB undergoes a conformational change to become active- is released from the membrane and effects numerous proteins- can activate/deactivate by its kinase activity
activated PKB promotes glucose uptake

Question 7

What happens when theres low blood insulin levels?

Answer 7

Foxo is localised in the nucleus-> binds to its promoter-> leads to increased production of hepatic insulin

Question 8

What happens when there’s high blood insulin levels?

Answer 8

Insulin binds to its receptor-> PKB activated-> phosphorylates FoxO proteins resulting in their translocation from the nucleus-> stop affecting gene expression

Question 9

What is promoter bashing?

Answer 9

Technique used to identify whether promoters etc. affect the transcription of downstream genes

Question 10

What things do PKB activate/inactivate?

Answer 10

FOXO- inactivated
Glucose transporter- activated
Glycogen synthase kinase- inactivated