At what blood glucose level is insulin produced?
At what blood glucose level is glucagon released?
Which cells in the pancreas are responsible for secreting insulin?
Which cells in the panreas release glucagon?
What are the basic stages in the synthesis of the insulin hormone?
It is synthesised in the RER of beta cells
First preproinsulin is formed
The C peptide is cleaved from this molecules leaving two polypeptide chains (A and B) linked by disulfide bonds
What is the name given to a very fast and short acting insulin preparation?
What is the name given to an ultra long acting insulin preparation?
What must Lispro be used in conjunction with for continuous insulin infusion?
A longer-acting insulin preparation
(it is useful for around meals)
Using Lispo, has a major disadvantage which is the fact it is antigenic
True or false?
It is not antigenic
Why is glargine so long lasting?
It precipitates in the subcutaneous tissue
How does glucose enter beta cells and what occurs when it does?
Phosphorylated by glucokinase
Why does a change in glucose concentrations above 5mM lead to a dramatic change in glucokinase activity?
The Km for glucokinase is around 5mM of glucose
If there is an increased metabolism of glucose within beta cells, there will therefore be subsequent increase of what in the cell?
What is the consequence of a raised intracellular ATP within beta cells?
ATP inhibitis KATP channels
This causes depolarisation
When a pancreatic beta cell is depolarised via high intracellular ATP, what is the outcome?
Ca2+ voltage gated channels will open
This causes secretory vesicles to fuse with the cell membrane and release insulin
Normally the release of insulin is __________
Normally the release of insulin is biphasic
Why are two phases of insulin release usually required?
Only 5% of insulin granules are ready for release at the initial period
The reserve pool must undergo preparatory reactions in order to be ready for release
What is the term given to the pool of insulin that is ready for immediate release?
Readily releasable pool
Which two proteins does KATP consist of?
- KIR - Inward rectifier subunit (Kir6)
- Sulphonylurea receptor - Regulatory subunit (SUR1)
KATP can be directly inhibited by which class of drugs?
Give two examples of drugs within the sulphonylurea drug class
What stimulates KATP and what is the outcome of this?
Insulin secretion is inhibited
Which drug class can be used alongside metformin as an adjunct to first line treatment for type 2 DM?
A mutation in what will lead to neonatal diabetes?
(this may lead to increased KATP activation or increase in numbers)
How can congenital neonatal diabetes be treated?
Mutations in which things may lead to congenital hyperinsulinism?
Which treatment may help congenital hyperinsulinism?
What is MODY?
Maturity onset diabetes of the young
What can cause MODY?
- Monogenic diabetes with beta cell genetic defect
- Familial form of early onset type II diabetes with defects in insulin secretion
- Mutations in at least 6 different genes other genes (there are around 150 genes)
What causes MODY2?
Mutations in the glucokinase genes
Impaired glucokinase function