16 - Endocrine pancreas and diabetes Flashcards
(51 cards)
What do beta-cells in the islets of pancreas produce?
Insulin
What is the major cell-type in the islet of Langerhans?
beta-cells (75%)
What is the second most common cell type in the islets of Langerhans?
alpha-cells (20%)
What do alpha-cells secrete?
glucagon
How do alpha- and beta- cells store their hormones intracellulary?
In membrane-bound vesicles prior to secretion (storage granules).
Each cell may contain up to 13,000 storage vesicles!
How are alpha- and beta- cells’ ultrastructure specialised for the role as endocrine cells?
Extensive rER
well-defined golgi apparatus
lots of mitochondria
well-define system of microtubules and microfilaments (very organised cell structure)
How many covalent disulphide bonds hold the A and B polypeptide chains of insulin together?
2
There are two inter-chain disulphide bonds in insulin, where is the third found?
Intra-chain disulphide bond within the A chain
Where in the cell are the disulphide bonds of insulin (proinsulin at this point) formed?
ER lumen
Where in the cell is the C peptide cleaved from the A and B chains of proinsulin, forming insulin?
Post-Golgi in secretory vesicles
Where in the cell are the ribsomomes that synthesise pre-proinsulin found?
Attached to the rER
What is the ‘pre’ part of pre-proinsulin and what happens to it?
It is a signal peptide that ensures that correct co-translational translocation (translocation from ribosome on outside of ER through membrane into the lumen of the ER)
What happens to the proinsulin inside the ER cisternal space?
It folds to ensure correct alignment of cysteine residues and that the correct disulphide bonds form
What two peptides are proteolytically cleaved from proinsulin inside the storage vesicles?
C peptide and a chain of four basic amino acids
Where is the C peptide and the chain of four basic amino acids found in proinsulin?
middle
What does the storage vesicle from beta-cells contain when it is released?
Insulin and C peptide - equimolar amounts
small amount of unchanged proinsulin
Why is C-peptide a useful marker of endogenous insulin release?
Because insulin and C-peptide are released from beta-cells into blood plasma in equimolar amounts
Why would you be interested in measuring plasma C-peptide levels in patients receiving insulin injections?
To monitor any endogenous insulin secretion
How is insulin transported?
Free in blood (not bound to a transport protein)
What complexes with insulin in storage granules inside the beta-cell?
Insulin forms a crystalline zinc-insulin complex
What are the major target tissues for insulin?
liver, skeletal muscle and adipose tissue (though insulin is required for the normal growth and development of most tissues in the body)
Where does insulin interact on the target cells?
Insulin receptors on the surface of target cells
What receptor family are insulin receptors a member of?
Tyrosine kinase receptor family
What are the short-term effects (sec/hours) of an increase in the concentration of insulin circulating?
Changes in the activities of pre-existing functional proteins such as enzymes and transport molecules in target tissues
