00:01
Let’s have a look at insulin synthesis.
00:04
Insulin is synthesized as a 110 amino acid long preproinsulin, composed of a signal peptide, depicted in orange,
a B-chain in blue, the connecting peptide in yellow, which is a C-peptide to be exact and lastly the red part, which is the A-chain.
00:23
The signal peptide is later cleaved off,
resulting in the formation of proinsulin.
00:29
Within the endoplasmic reticulum, three disulfide
bonds are formed between cysteine residues.
00:36
Proinsulin is then transported to the Golgi apparatus,
where the C-peptide is cleaved off.
This process converts proinsulin into mature insulin,
which consists of the B and A chains only.
00:51
Keep in mind that C-peptide is only produced during endogenous insulin production.
Therefore, in the case of exogenous insulin, which is taken by diabetics, no C-peptide will be found in the blood.
01:06
Exogenous insulin is typically manufactured in
recombinant DNA technology using Escherichia coli.
01:13
This type of insulin does not contain C-peptide, this allows the differentiation between true endogenous and false exogenously produced hypoglycemia.
01:25
Insulin.
01:28
Insulin forms usually
of what glucagon is.
01:33
It's formed also in the islet
and specifically
in the beta cells.
01:38
It is also a peptide
hormone similar to glucagon.
01:43
It is clear about 50%
by the first path.
01:48
This is an important process because again
it's going to mean that
insulin is not around in
the circulation very long.
01:56
In fact it's half life
is only 3 to 8 minutes.
02:03
Importantly what we have
produced at the same time
as the peptide hormone
insulin is something
called C-peptide.
02:14
Don't get this mixed up
with C reactive peptide.
02:17
This is just C-peptide.
02:20
C-peptide is when passed
through this first pass
system in a slower
time frame.
02:29
Therefore, it has
a longer half life.
02:32
About 35 minutes.
02:35
If you compare 35 minutes
half life versus
a 3 to 8 minute half life,
you can see that C-peptide stays in the circulation longer.
02:45
How is that useful
for you clinically.
02:47
How useful is that,
you can use C-peptide
if you measured in the blood
as an index for how much
insulin is being secreted.
02:59
Because insulin is not
going to be around long
enough to really measure
it's concentrations.
03:04
But if you measure
C-peptide, you know it's
produced in a
1 to 1 ratio.
03:09
Therefore, if C-peptides
goes up, insulin has to go
up and vice versa.
03:16
You can see how this
break down of this process
works.
03:19
If you see this
polypeptide being formed.
03:22
And there's a cleave
that happens, that forms
C-peptide and insulin.
03:28
So they'll be making
this preformed proinsulin
peptide.
03:34
You cleave a certain spot,
leaving C-peptide
and insulin as your two
different secretory substrates.