Insulin and Glucagon Flashcards
How is insulin synthesised?
Preproinsulin is synthesised in the ribosomes of B cells.
It enters the ER and is cleaved by enzymes to become proinsulin.
Proinsulin is packaged in the golgi into secretory vesicles and cleaved again and it loses the middle āCā chain, the A and B chain are held together by disulfide bonds.
How is insulin released?
Glucose enters the B cell via GLUT2 transporter.
Clucose is converted to G6P by glucokinase and then undergoes metabolism to produce ATP.
The sulfonyl-urea receptor subunit on ATP-dependent K+ channel sense the increase in ATP and closes K+ channels.
This causes the cell to depolarise, opening Ca2+ channels and calcium enters the cell.
Increased calcium in the cell causes insulin secretory vesicles to be released via exocytosis.
What is glucagon secreted in response to?
Low glucose.
How does insulin exert its effect?
It binds to insulin tyrosine kinase receptors on the surface of target tissues (liver, muscle, fat)
This causes a conformational change in the receptor causing autophosphorylation - initiating an intracellular signalling cascade.
Intracellular signalling cascade allows amplification of the hormone signal.
Phosphorylates Protein Kinase B - which is responsible for all the effects of insulin.
This leads to translocation of GLUT4 transporters to the cell membrane which transports glucose into the cell.
List what insulin stimulates and inhibits?
Stimulates;
- Glucose transport
- Glycogen synthesis
- Fatty acid synthesis
Inhibits;
- Lipolysis
- Gluconeogenesis
How does glucagon exert its effect?
Binds to a G-protein coupled receptor (GPCR) found in hepatocytes.
Increases cAMP.
cAMP stimulates cAMP-dependant Protein Kinase A.
What is normal plasma glucose before and after a meal?
4-5mM before a meal.
8-12mM after a meal.
List the actions of insulin?
Promotes glycogen synthesis in liver, glycogen uptake in muscle, glucose to be taken up by adipose tissue, and synthesis of fatty acids and triglycerides.
It inhibits gluconeogenesis and glycogen breakdown in the liver.
List the functions of glucagon?
Promotes glycogen breakdown in the liver and gluconeogenesis.
Inhibits glycogen production and glucose uptake by tissues.
What is the function of glycogen in the liver?
Stored for blood glucose maintenance.
What is the function of glycogen in muscle?
Stored for local energy production, so is only used by the muscle itself.
What enzymes does insulin promote in liver glycogen metabolism in the fed state?
Glucokinase and glycogen synthase.
(inhibits G6Pase and glycogen phosphorylase).
What does insulin promote in muscle glycogen metabolism in the fed state?
Glycogensynthase
(inhibits glycogenphosphorylase)
Also promotes Glut4 transporter so more glucose is taken into cells.
What does Glucogon and (Nor) Adrenaline promote in liver glycogen metabolism in the fasted state?
Why does adrenaline also stimulate this?
Promotes G6Pase and Glycogen Phosphorylase.
(Inhibits glucokinase and glycogen synthase).
Adrenaline/noradrenaline stimulate the same cAMP pathway.
What does (Nor) Adrenaline promote in muscles in glycogen metabolism in the fasted state?
Why does glucagon not work here?
Stimulates Glycogen Phosphorylase.
(inhibits glycogen synthase and Glut4 transporter).
No glucagon receptor in muscle.
