Insulin

Question 1

How is insulin made

Answer 1

Prepro insulin is cleaved to proinsulin then cleaved by endopeptidases to removed the C peptide and form insulin from A and B chains with 2 disulphide bonds

Question 2

What triggers insulin secretion, the full process

Answer 2

Glucose enters beta cells in the pancreas via GLUT 2 transporter it is phosphorylated by glucokinase into G-6-P which then undergoes glycolysis and the TCA cycle resulting in ATP production, this closes KATP channels causing a build up of intracellular potassium causing depolarisation of the cell membrane, opening voltage gated Ca2+ channels, calcium enters and stimulates insulin release

Question 3

What components make up the KATP channel

Answer 3

Inward rectifier (KIR6) + Sulphonylurea (SUR1)

Question 4

What is glucokinase and its characteristics

Answer 4

Hexokinase isoform found in the liver and pancreas, has a high Km for glucose so requires a higher glucose concentration for activation (acts as a sensor)

Question 5

Describe the biphasic release of insulin

Answer 5

1st phase: RRP (ready releasable pool-5%)

2nd phase: Insulin granules require manipulation before release

Question 6

Describe the insulin signalling pathway

Answer 6

Insulin binds to alpha subunit of RTK receptor causing dimerisation and autophosphorylation of the tyrosine residues in the beta subunits activating the PI3K pathway + MAPK pathway

Question 7

What does activating the PI3K pathway stimulate

Answer 7

Activates PKB/ALT which activates GLUT 4 allowing glucose entry into fat and muscle cells and inhibits hepatic glucose synthesis and activation of glycogenesis

Question 8

What does activating MAPK pathway stimulate

Answer 8

Activates RAS resulting in cell growth