Endocrinology | Pancreas: Insulin Function — Transcript

All right, engineers, in this video, we're going to talk about the pancreas, but specifically, we're going to focus on the hormone insulin.

So, let's take a look here at the pancreas.

If you look at the pancreas, the pancreas is actually referred to as a heterocrine gland.

Okay, so what is it referred to as?

It's referred to as a heterocrine gland.

So, what it means to be heterocrine is it's made up of two different types of tissues, right?

One, it's just going to have this endocrine producing tissue.

And the other one is it's going to consist of a exocrine producing tissue.

Now, the endocrine producing tissue is actually made up of two things.

It's actually made up of alpha cells, okay, alpha cells and beta cells.

These are the two more significant ones.

There is more than just alpha cells and beta cells.

There's even delta cells and F cells and PP cells.

There's a whole bunch of different types of cells.

Okay, so these endocrine portion is the alpha cells and the beta cells.

Now, the alpha cells are responsible for secreting a hormone referred to as glucagon.

Okay, you can remember that because there's an A in glucagon and there's an A in the alpha.

The beta cells are responsible for secreting insulin.

Okay?

And insulin in general, if I were to just categorize insulin as what type of hormone he is?

He is responsible for trying to be able to bring our blood glucose levels down.

So, he responds, so in other words, his stimulus.

What's his stimulus?

His stimulus is hyperglycemia.

And as a response to that hyperglycemia, his job is to be able to bring the blood glucose levels back down.

Okay, so his responsibility is to be able to bring the blood glucose levels back down.

Now, glucagon, his is the exact opposite.

You can remember that by it's released whenever glucose is gone.

All right, it's easy way to think about it.

I just I think about there being a gone there, right?

So, glucagon is released whenever your glucose is gone or whenever you have low blood glucose levels.

So, they refer to it as hypo glycemia.

Okay?

Now, what's normally, uh, to kind of get an idea here?

What's a normal blood glucose range?

Normally, a blood glucose range ranges from about 80 to 120 milligrams per DL.

This is an average blood glucose level.

Okay, so an average blood glucose levels is just going to range from about 80 to 120 milligrams per DL.

All right, so if you're below 80 milligrams per DL.

That's referred to as hypoglycemia.

Whereas, if you're above 120 milligrams per DL, that's referred to as hyperglycemia.

Okay, so again, below 80, hypoglycemia, above 120, hyperglycemia.

And kind of an idea here is you do have a little bit of buffer here.

You can maybe even consider about 70 milligrams still to be within the normal range.

But generally, I'm just going to go with about 80 to 120.

Okay?

But it can go about to about 70.

All right, now, the exocrine portion, we're going to talk about that in the digestive system.

But just to highlight it, the exocrine portion is actually made up of what's called the acini.

And this is the one that's releasing pancreatic juice, rich in digestive enzymes and bicarbonate.

Now, the endocrine portion that we talked about with the alpha cells and the beta cells.

If you look here, we have alpha cells and beta cells, and like I told you, there is other cells like delta cells and PP cells and F cells.

They're actually aligned in like a cluster.

So, imagine this cluster of cells in that area, okay?

And it only makes up about 1% of the entire pancreas, right?

So, 99% of it is acini.

So, again, how much percent of it is acini?

About 99% is acini, and about 1% of it is this structure.

Which we call the islets of Langerhan.

This right here is going to be the endocrine portion of the pancreas.

Okay, it's these little clusters called the islets of Langerhan.

Now, the islet of Langerhan, which I told you, has the alpha cells and the beta cells.

But we're primarily in this video going to focus on insulin.

So, which cells are we going to really be looking at?

We're going to be looking at the beta cells.

Okay, so now we're going to zoom in here into a beta cell.

So, this right here, I'm zooming in on a beta cell.

Now, beta cells, like I told you, are responsible for being able to release insulin.

Right?

They're responsible for releasing insulin.

Now, with the beta cells, they're actually going to use their DNA.

So, inside of the DNA, there's a specific gene.

Let's say here's the gene right here.

You know, genes, they actually undergo transcription.

And when they undergo transcription, they get converted into mRNA.

And then mRNA comes out here into the cytoplasm.

And what does it do?

It meets with a ribosome.

So, let's say here's a ribosome right here, and here's a ribosome on the other side of it.

Right, small and large ribosomal subunit.

That mRNA will come in here, right?

And it'll get read by the ribosomes, and then what, you'll synthesize a protein.

So, out of this, there'll be a protein synthesized.

Now, generally, what has to happen is he has to go to the rough ER.

So, generally, he'll go to the rough ER, so let's say I just draw a generic rough ER here.

So, it has to go to what is this structure here called the rough endoplasmic reticulum.

And then it undergoes certain types of modifications.

Then after that, it has to go to another structure.

Let's say it goes to another structure, and this next structure is called the Golgi apparatus.

So, then it goes to the Golgi.

And in the Golgi, he gets packaged, right?

And whenever he comes out of this, look what he comes out as.

So, out of the Golgi, I'm now going to have this fully packaged insulin.

Okay?

So, now what would I have in here?

I will have insulin.

Now, insulin is actually made up of Now, generally, what happens is whenever you have a hormone, you start with what's called proinsulin.

And then it undergoes specific types of cleaving processes in the rough ER, modifications, packaged and stored in these vesicles.

So, now I have insulin in here.

But I also have another important peptide.

Which I should mention here.

This other peptide is called C-peptide.

And I'll explain that in a second.

So, we've synthesized our insulin.

Our insulin is sitting in these vesicles.

So, not only there's just one vesicle, there's many, many different types of vesicles here.

Consisting of this insulin.

So, let's say I just draw here for the sake of it, three vesicles with insulin and C-peptide.

So, here's insulin, here's insulin.

And I'm just going to represent C-peptide, which is just a C here.

So, C, C-peptide.

Okay?

They're in these vesicles.

They're packaged in there.

And they even have zinc in there, too.

Now, look what happens.

What did I tell you these beta cells are responding to?

What's their stimulus?

Their stimulus was hyperglycemia.

So, whenever your blood glucose levels are elevated above this normal range of about 120 milligrams per DL, right?

So, the blood glucose levels are high.

Let's represent that then.

Let's show here the blood glucose levels are really high.

I'm going to represent glucose as this G here.

Okay?

On the pancreatic beta cell, it has these specific types of transporters.

You see this blue transporter right here?

This blue transporter is actually called a GLUT2 transporter.

What the heck is GLUT2?

GLUT2 means it's a glucose transporter type 2.

And I know type 2 might be like, ah, who cares about that?

It's very significant because that means that if it's a GLUT2, it's insulin independent.

It doesn't need insulin.

So, in other words, this glucose is going to move in here into this pancreatic beta cell.

And if you have a lot of glucose, what does glucose undergo when it gets into the side of the cell?

You know, it undergoes glycolysis.

So, let's say here's glucose, he'll eventually get converted into glucose 6-phosphate, and then eventually he'll get converted into pyruvate.

If we just keep going down here, and then eventually goes to acetyl-CoA.

And then from acetyl-CoA, what happens?

It goes through the Krebs cycle.

And out of the Krebs cycle, you produce NADH's and FADH2's and all that freaking good stuff, right?

Where do these guys go?

Look where they go now.

The NADH's and the FADH2's that you produce, they go to the mitochondria.

And when they're at the mitochondria, what happens?

They actually go through the electron transport chain, right?

And out of the electron transport chain, what do they produce by oxidative phosphorylation?

ATP.

Right?

Because that's generally what happens, glucose undergoes glycolysis, then it undergoes transition step, undergoes Krebs cycle.

And makes these NADH's, these FADH2's, and then it gets taken to these transporters.

Because all of this right here, pyruvate, acetyl-CoA, Krebs cycle, and even these formations of these guys.

It's all occurring here in the mitochondria.

And then it's producing ATP.

Why is that significant?

You see this like a channel right here?

This channel right here is specifically for potassium.

So, this is a potassium channel.

So, potassium loves to be able to move through this channel.

So, let's say here's your potassium.

But guess what?

There's a little pocket here for the ATP.

So, the ATP literally comes in here and binds.

When ATP binds onto this channel, it closes the channel.

So, it inhibits the channel and closes it.

So, now this channel is closed.

So, let's represent this channel as being closed now.

Okay, potassium can't get out.

If potassium can't get out, he tries to be able to escape, but he can't escape.

What happens to these positively charged ions?

You start accumulating a lot of potassium ions.

Which are positively charged.

When you accumulate a lot of positively charged ions, what happens to the cell membrane potential?

It becomes very, very positive.

And whenever this actually occurs, it increases and tries to bring up the the membrane potential.

So, your positive membrane potential, right?

Whenever this positive membrane potential occurs, that stimulates these pink channels right there.

What are these pink channels for?

These pink channels are for calcium.

And calcium's going to start flooding in to this beta cell.

Why is that important?

Let me show you.

You know, on top of the insulin, there's a specific protein.

On top of the cell membrane, there's a specific protein.

Guess what that calcium ion does?

The calcium ions, I'm going to represent that in red here, are linking together the synapto proteins.

It's linking together the synapto protein on the vesicle containing insulin and the synapto protein here on the membrane.

When that happens, what happens to this actual vesicle and the cell membrane?

They fuse.

And whenever this fuses, it opens up into the actual blood.

And what does it release out?

It releases out the insulin.

So, now what do we release out here?

We released out here insulin.

You'll also release out C-peptide.

Remember, I told you, you release C-peptide.

And for the heck of it, you also release another molecule called amylin.

Okay?

And this is significant in type 2 diabetes.

I'll talk about it whenever we get there.

But now, these molecules are going to get moved into the blood.

Okay, so now in your bloodstream, you have insulin.

Which is the one that we're going to focus on.

Now, I told you, I'd give you a little brief little thing about C-peptide.

So, let me talk real briefly about C-peptide.

C-peptide is important because he's a good way to be able to monitor insulin levels.

Right?

So, because you can monitor C-peptide, it kind of gives you a decent idea of someone's insulin levels.

So, that's what they can use C-peptide for.

Is being a way to monitor someone's insulin levels.

Why would that be a good monitor of insulin levels?

Because whenever you release insulin, guess what else you release?

C-peptide.

And amylin is actually, if you produce too much insulin, these amylin proteins can cause amyloid deposits.

And actually cause destruction of the beta cells.

And that can lead to that's a usually a cause of type 2 diabetes mellitus.

All right, so this insulin.

What is he going to go and do now?

That's what we want to know.

We want to know what the heck is insulin going to do over here?

Okay?

So, let's see what he's going to do.

Let's go ahead and first see what he does on the liver.

Okay, so let's show this insulin.

This insulin is going to come over here and it's going to bind onto a receptor.

Now, we didn't really talk too much about this receptor.

You probably haven't seen it too much yet.

But it's called a tyrosine kinase receptor.

We're not going to talk about it.

We're not going to go over the pathway.

It's not necessary.

But it's a tyrosine kinase receptor.

Okay?

In other words, whenever insulin binds here, so let's say that I represent insulin with an I.

Whenever insulin binds there, it stimulates specific phosphorylation of tyrosine residues.

And the overall result is you activate this intracellular messenger called PI3K and AKT.

And AKT is just protein kinase B, really.

Why am I telling you this?

When insulin does this, this enzyme is very, very important within the liver.

Okay?

What did I tell you was wrong with the blood?

What was really, really high in the blood that we showed before?

You have really, really high blood glucose levels.

The whole goal of insulin is to bring those glucose levels down.

So, what this actual insulin does is now, remember, I told you about the liver, right?

You got the liver.

You see these these blue proteins?

It's the same ones that were on the pancreatic beta cells.

But I was very particular about the type of GLUT receptor it was.

It's GLUT2.

What does that mean?

That means that this insulin, I'm sorry, that GLUT receptor is independent of insulin.

So, in other words, insulin doesn't control that GLUT receptor.

Glucose can move in at its own constant rate.

Once glucose is brought into the liver cell, that's where insulin can be of use.

Okay?

What insulin's going to do is it's going to convert this glucose into a specific molecule.

It's going to take glucose and it's going to polymerize the glucose into glycogen.

Okay?

So, that's one thing it's going to do.

One thing it's going to do right away is it's going to help to stimulate these PI3K and AKT.

The protein kinase B.

It's going to stimulate glycogenesis.

That's one mechanism.

You know what else it can do?

It can take this glucose and help to be able to convert it into pyruvate.

So, it can actually work through specific types of glycolytic enzymes.

And takes and converts those glycolytic enzymes and makes them active to help to be able to form pyruvate.

Through specific types of phosphatase activity.

Okay?

So, again, one more time.

Insulin's binding onto the liver, activating tyrosine kinase receptors.

Forming these intracellular messengers like AKT, protein kinase B, he's called.

Who helps to be able to convert glucose into glycogen.

And helps to be able to convert glucose into pyruvate.

By activating glycolysis.

That's one way.

And what is that doing?

That's yanking the glucose out of the blood and converting it into different storages.

Because what's the end product?

If you keep following pyruvate, he goes to acetyl-CoA, right?

And then we know acetyl-CoA goes to the Krebs cycle, who goes to the electron transport chain.

And produces ATP.

So, we're going to use this to get some energy, too.

Okay?

All right.

So, that's the two mechanisms.

Let's actually outline that.

One mechanism is forming glucose into glycogen.

What is that called when you take glucose and convert it into glycogen?

That is called glycogenesis.

Okay?

Okay, that's one mechanism.

We also said the other mechanism was taking glucose and converting it into pyruvate.

Which will then go through its other steps.

What is this step here called?

This is called glycolysis.

Okay?

So, that's what it's doing, it's stimulating glycolysis and glycogenesis.

All right.

That's what it's doing in the liver.

Let's see what it's doing over here in the muscles.

So, let's take this insulin and let's follow this insulin out here.

Okay, so this insulin's going to come out to this area.

And it's going to come and act on this receptor.

Again, a tyrosine kinase receptor.

Now, when it activates the tyrosine kinase receptor, I'm probably going to get on you guys' nerves.

This is called a GLUT4 transporter.

Why am I telling you it's GLUT4?

Because GLUT4 is dependent upon insulin.

So, normally, this is bringing glucose in.

But what this insulin's going to do is it's going to activate these protein kinase B.

This protein kinase B is going to come over here and activate this GLUT4.

It's going to stimulate it.

Maybe by phosphorylation reactions.

If it stimulates GLUT4, what is that GLUT4 going to do?

It's going to become hyperactive.

And what was really high out here in the blood again?

Glucose.

So, what's glucose going to do?

It's going to start funneling into this muscle cell.

If it starts funneling into this muscle cell, what can the actual insulin do within that muscle cell with that glucose?

Remember, I told you, it can take the glucose and eventually convert it into pyruvate, right?

And then from pyruvate, where can pyruvate go?

He can go to acetyl-CoA.

Who goes into the Krebs cycle?

Who goes to the electron transport chain?

And produces ATP.

Right?

What is this protein kinase B?

This whole complex from insulin doing?

It's stimulating that glycolysis pathway.

So, over here, what is it doing?

One thing is it's enhancing this GLUT4 activity to bring glucose into the cell.

So, it's enhancing this step right here.

It's called it's increasing glucose uptake.

Which is a fancy word for just being able to say.

Bringing glucose into the cell.

It's increasing the rate at which glucose is being brought into the cell.

And it's stimulating the conversion of glucose into pyruvate.

What's that called?

That is called glycolysis.

Okay?

You know, it's not done at that, too.

It loves to be able to do other things.

He loves to help out.

That's what insulin does.

Insulin's a great helper.

So, what insulin does is, since we already know that it does this, I'm going to get this out of the way.

Because we're only really concerned with the pyruvate pathway.

But it can that just understand that that pyruvate can go to acetyl-CoA and be utilized for ATP.

Look what else it does.

There's other transporters over here on the cell membrane.

So, let's say here's another transporter.

And this transporter is specific to specific types of amino acids.

So, you know, amino acids are really, really important for making proteins, right?

Especially within the muscle cells.

So, you know what this actual guy does?

He comes over here and he stimulates this red protein channel.

What's that red protein channel?

This is called an amino acid channel.

Now, you know, whenever you're eating, so right when you eat, they call it the fed state, right?

So, or the absorptive state.

Right when you're eating, that's when your glucose levels and your amino acid levels in the blood are really, really high.

So, what's going to be really, really high out here?

If I were to represent it in a different color.

Let's say I do it in brown.

Okay, so let's say out here in the blood, you're going to have high amino acid levels in the blood.

Why is it high?

Because you just got done eating, right?

So, right when you're eating, so when you're in the fed state or the absorptive state.

Your amino acid levels within the blood are very, very high.

Insulin takes that to his advantage.

And he stimulates these amino acid channels.

And helps to be able to pull these amino acids into the muscle cell.

So, it stimulates that.

So, what's that called whenever you're increasing the activity of these amino acid channels?

It's stimulating amino acid uptake.

Okay?

Then look what else it's doing.

He's not done.

You know, amino acids are the building blocks, let's say I represent these dots as amino acids.

If I take these amino acids and I string them together by making peptide bonds.

So, now I'm going to represent those little dots as a whole component of this large, large molecule.

Which is called a protein, right?

So, proteins are basically the the they're actually the polymers, right?

Because these are the monomers, amino acids are the monomers.

So, they're the building blocks of proteins.

What this actual insulin does through these protein kinases is it stimulates this process.

What is this called when you're taking amino acids and converting it into proteins?

This is called protein synthesis.

Man, this hormone is is really, really getting around, huh?

So, he's stimulating protein synthesis and amino acid uptake.

He's stimulating glycolysis.

He's stimulating glucose uptake.

Only through the GLUT4 transporters.

He's stimulating glycogenesis within the liver.

He's also stimulating glycolysis within the liver.

You know what else he can do inside of the muscle?

He's not done.

He can take that glucose and he can convert that glucose into glycogen.

So, he can also stimulate this reaction here.

And what is that called?

That's called glycogenesis.

Okay?

Now, if you can think about it.

There was high glucose levels in the blood, and I told you that there was also high amino acid levels in the blood.

And if you really want to think about it, it also has high fatty acid levels in the blood.

Now, technically, some of these fatty acids can also get taken up by the actual adipose tissue.

And utilize.

So, if I were to represent that, too, technically, these fatty acids.

They can actually be brought into the cell.

And insulin can actually help to stimulate some of these fatty acids.

To be converted into triglycerides.

Okay, so again, because you just remember, insulin is secreted whenever you're eating.

Okay, during the absorptive state.

So, these fatty acid levels in the blood will go down.

The amino acid levels in the blood will go down.

Why?

Because insulin is stimulating the amino acid uptake.

The glucose levels in the blood will go down.

That's his whole effect.

So, it's beautiful to understand that, and you can see now that whenever insulin is actually deficient.

Or whenever it's produced in large amounts, it can cause drastic effects on the body.

Okay, and we'll cover that in diabetes, and we'll also talk about them when we talk about insulinomas.

All right, engineers, we covered a lot of information in this video.

I hope it all made sense.

I hope you guys enjoyed it.

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