Insulin Biochemistry Flashcards
What cells secrete insulin?
Pancreatic beta cells
What is the location of the pancreatic beta cell?
In the pancreatic islets. The are located close to the blood vessel to allow them to detects the blood glucose concentration
How is insulin formed?
- Synthesised in the RER of the pancreatic beta cells as a larger preprohormone - PREPROINSULIN
- Cleaved to form insulin by Ca2+ dependent peptidases
What is the structure of the insulin hormone?
Two amino acid chains joined by two disulphide bridges
Where is insulin stored?
Within granules in the betacells until it is secreted into the bloodstream by exocytosis in response to the appropriate stimulus.
What is the main function of insulin?
To lower blood glucose concentration
How was the diagnostic criteria of diabetes mellitus determined?
They likelihood of development of diabetic retinopathy
What is the result of too much insulin?
Hypoglycaemia
What is the process of insulin secretion?
- Glucose enters the beta cell through GLUT2 Transporter and is phosphorylated by glucokinase
- The change in concentration leads to a dramatic change in glucokinase activity
- The increased metabolism of glucose leads to an increase in intracellular ATP concentration.
- This ATP inhibits the ATP-sensitive K+ channel and prevents K+ from leaving the cell. Depolarisation occurs.
- Depolarisation results in the opening of voltage gated Ca2+ channels.
- The increase in intracellular Ca2+ leads to fusion of secretory vesicles and the release of insulin
What occurs in relation to insulin in type 1 diabetes?
The beta cells are mostly lost
What level of blood glucose causes the beta cells to secrete insulin?
Above 5mM
This is because glucokinse is the main glucose phosphorylating enzyme and its Km lies close to 5mM
Why is the release of insulin biphasic?
The first phase prevents a sharp increase in blood glucose.
The second phase is more tuned to the body’s insulin requirement and is released in relation the the glucose intake
What are readily releaseable pools of insulin?
5% of insulin granules are immediately available for release in response to an increase in intracellular calcium
What are the two proteins in the KATP channels?
Kir6 (Inward Rectifier Subunit)
SUR1 (Sulphonylurea Receptor Regulatory Subunit)
What is the function of the SUR1 subunit of the KATP channel?
To regulate K+ flow