In order for us to truly understand endocrine
pancreatic pathology, it is imperative that
we have a good understanding of pancreatic
function and hormones.
The endocrine pancreas itself, we have Islet
cells and our focus in this entire section
is going to be dealing with insulin and its
effects on various organs throughout the entire
The picture here is showing you the pancreas
and beta Islet cell.
We do something called immunohistochemistry
in which it then identifies the insulin within
the beta Islet cell.
On this table, a brief review of various hormones
that are important for you to know from the
The Alpha cells, measly 10 percent, but, my
goodness, responsible for releasing an important
hormone called Glucagon.
In pharmacology, you have heard of some of
these GLP-1 analogues, things that you want
to keep in mind.
Dorsally derived, embryologically anterior
head, body and tail.
Beta cells comprise majority of your Islet
cells at 70-80 percent, responsible for releasing
insulin and every time there is insulin being
released, do not forget endogenously, from
your beta Islet cell, you are going to release
your C peptides.
The D cells, 5 percent, release Somatostatin.
There is something called F cells, Pancreatic
Let’s go to talk about that insulin.
Whenever-Whenever it is being produced in
your beta Islet cells, it goes through the
process of preproinsulin, proinsulin and insulin
and you notice here at the bottom, a C peptide
and that C peptide to you means that every
time insulin is being churned out of a beta
Islet cell into a circulation.
It is also along with it releasing C peptide.
The measuring of C peptide came to use for
clinically to distinguish between that insulin
which is being produced endogenously, example
Insulinoma, versus that type of insulin in
which maybe perhaps your patient is taking
exogenously minus the C peptide.
Let’s go ahead and talk about what promotes
What are we looking at here is in fact once
again a beta Islet cell.
The glucose binds the gluc… glucose 2 transporters
in the beta cells and these glucose 2 transporters
are absolutely insulin independent, they have
What is this cell that we are looking at here?
A beta Islet cell.
Where in the body are you?
In the pancreas.
It is responsible for releasing insulin.
If it is responsible for releasing insulin,
how could you have receptors that are dependent
Doesn’t make sense.
At the top left corner, you notice a flux
of glucose coming into the cell and that is
through your glucose transporter 2, insulin
The glucose, close your eyes, the glucose
will go through a biochemical process known
as your glycolysis, just like you would in
any healthy cell, right?
And any healthy cell, the glucose will go
through, well, we as humans, you carry out
exhale, we breathe, bringing in oxygen and
that is aerobic glycolysis.
Through aerobic glycolysis produce pyruvate
going to [Inaudible 00:03:48] into the electron
transfer chain and what did you produce?
ATP, right, ATP, aerobic glycolysis, keep
that in mind.
Let’s keep going.
What are we trying to do?
Objective is to release insulin from a beta
You see the right lower quadrant of this cell?
They are remaining dormant right now, who
is remaining dormant?
The vesicles, the vesicles remaining dormant
and they are filled with insulin.
The objective of this entire discussion is
how do we release insulin when we consume
a piece of chocolate, carbohydrates, this
is how we are doing it.
That ATP that was just produced, look what
It blocks the potassium channel, pause.
When you, normally, [Inaudible 00:04:46] potassium,
move into out or out to in…
Normally, it moves from in to out, right?
What charge does potassium have?
So, you… this ATP amazingly produced by
glucose and through aerobic glycosylation,
so on and so forth it, will block the potassium
So, therefore, potassium is trapped within
Hmm, what kind of charge?
A positive charge.
If you increase the positive charge within
the cell, simple, simple physiology that you
learned way back when, when you increase the
positive charge what then happens?
You create depolarization.
When it creates depolarization, you then hit
What do you do when you hit threshold?
All or none theory, remember actual potential.
An actual potential has been generated by
blocking the potassium channel and it doesn’t
want to leave.
Is that important?
Is it just all crazy by chemical details that
I am giving you is irrelevant?
Not at all.
There is a drug that blocks exactly where
you see that ATP.
It is called sulfonylurea, right?
Next, that potassium is blocked.
When it does, it creates your potassium that
SU that you see there in green, the abbreviation
stands for sulfonylurea drugs.
That’s exactly how they work.
Now, what kind of patient will be taking sulfonylurea,
type 1 diabetic or type 2 diabetic?
Obviously, type 2.
A type 1 diabetic doesn’t have insulin to
So, if the insulin isn’t there, how in the
world is this drug even effective?
It is not, use common sense.
So, type 2 diabetic using sulfonylurea, whenever
you give sulfonylurea, what is the huge side
effect that you are always worried about?
Uh-oh, I might be releasing too much insulin
from the pancreas and the patient may suffer
Here you go, this is why.
And we are not quite done yet, are we?
No, no, no.
So far, we have created an actual potential,
whenever an actual potential is being generated,
then you will then open up, here you go, down
at the lower bottom, we are going to open
up these Voltage-gated calcium channels.
Doesn’t this sound an awful, awful lot like
your neuromuscular junction?
That it does.
Here comes the calcium, here comes the calcium,
here comes the calcium, fluxing in, massive
influx, what do you think this calcium is
going to do?
It is going to then take these dormant vesicles
that you see in the lower right quadrant,
it is going to take these vesicles and fuse
it with the membrane, but this time, the vesicles
Insulin, not acetylcholine, this is not the
neuromuscular junction, but my goodness, similar
in behavior and then out will then come the
Out will then come the insulin and what does
It is then going to regulate the amount of
glucose in circulation because you just took
a piece of chocolate, you just had an appetizer
with bread, whatever it may be, of course
you are going to release insulin.