Biochemistry of insulin Flashcards
Where is insulin synthesised?
The rough endoplasmic reticulum of the pancreatic beta cell
What does insulin consist of?
Two polypeptide chains linked by disulphide bonds
What is the initial form of insulin synthesised?
Preproinsulin - contains an additional signal peptide and connecting C peptide
Why is human insulin used instead of pig or cow insulin despite similar peptide structure?
Avoids antibody formation
How does glucose enter the beta cell and what happens next?
Through GLUT2 transporter
Phosphorylated by glucokinase to glucose-6-phosphate to enter glycolysis
How does increased intracellular concentration of glucose in the pancreatic beta cell lead to release of insulin?
Glucose entering metabolism causes an increased intracellular concentration of ATP
ATP inhibits the K+/ATP channel, causing cell membrane depolarisation
This opens the voltage gated calcium channel, increasing [Ca2+]
Secretory vesicles fuse with cell membrane to release insulin
Why is the release of insulin biphasic?
There is prestored insulin ready for secretion immediately - 1st phase
There is a delay in the rest of the insulin release as time is taken to prepare more - 2nd phase
What are the two subunits on the KATP channels?
Kir6.1 - pore subunit
SUR1 - a sulphonylurea receptor, regulatory subunit
What is MODY?
Maturity onset diabetes of the young
Referred to as ‘monogenic diabetes’, this is a genetic mutation that causes defects in the beta cell function
What is the structure of the insulin receptor?
A dimeric tyrosine kinase
Has two extracellular alpha subunits and two intracellular beta subunits linked by disulphide bonds
How does insulin activate the catalytic activity of the receptor?
Binds to alpha subunits
Causes beta subunits to autophosphorylate
What happens after the beta subunits of the insulin receptor are autophosphorylated?
Insulin receptor substrates (IRS) are phosphorylated
What is the role of phosphorylated IRS in the uptake of glucose into cells?
Activates the RAS/MAPK pathway and gene expression
Activates PI3K, PKB, and glycogen synthesis
What does PKB do in the insulin signalling pathway?
Stimulates GLUT4 transportation to the membrane to allow glucose uptake
Where are ketone bodies formed?
In liver mitochondria, formed from acetyl-coA from beta-oxidation
