Insulin Signalling
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What is leprechaunism?
Usually fatal within two years of life Big ears, large hands and feet Decreases amount of subcutaneous fat and muscle mass is seen Hair overgrowth
What is Rabson Mendenhall syndrome?
Skin and teeth abnormalities Hair overgrowth Pineal Hyperplasia
Where is insulin made?
In the beta cells of islet of langerhans in the pancreas
What are the immediate and long term effects of insulin?
Immediate = glucose uptake from the blood in to muscle cells and adipocytes (1 minute) Longterm = increased expression of liver enzymes that synthesis glycogen and of adipocytes that synthesise triacylglycerols (2 hours)
Describe the steps of how insulin is matured
It undergoes proteolytic cleavage and is held together by sulfide bridges proinsulin -> insulin
What does insulin result in?
IRS activation
What is IRS?
Insulin receptor substrate Contains a phosphotyrosine binding domain (PTB) Highly phosphorlyated by the insulin receptor Then acts as a docking site for many other proteins eg GRB2
What does GRB2 activate?
The RAS pathway
What two pathways does insulin signalling use?
Ras Pathway Ras Independent signalling pathway
Describe the steps in the Ras independent signalling pathway
1) Insulin binds to receptor = autophosphorylation 2) IRS binds 3) PI3 kinase binds to IRS and phosphorylates so PI3 kinase is recruited to the membrane 4) It then phosphorylates