Hormonal regulation of metabolism
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Production of insulin and glucagon
- [Voiceover] As you can see on this gentleman right here, he's got a liver, and then this organ down here is referred to as the pancreas. Now the pancreas sits in the retroperitoneum which relative to the liver, which sits in the peritoneum, or in the abdomen, the pancreas is found to the back and to the left, to the back and to the left. And what's distinctive about the pancreas is it's blood supply. And so we can go through that in a little more detail after I blow up the pancreas right here and move it over just a little bit. Now the pancreas is like most organs, in that it receives oxygen rich arterial blood flow and gives off oxygen poor blood flow through the venous system. So this is the venous blood right here. And this is the arterial blood. But in addition to these two things, the pancreas also receives blood flow from the intestine, which I can draw right here. The small intestine will deliver unique nutrient rich blood through the pancreas and this is nutrient rich blood through the portal venous system. This is the portal venous blood flow. And once this nutrient rich blood flows through the pancreas it will trigger hormone release. Hormones such as insulin and glucagon and that'll actually be released into the portal venous blood and travel along with the rest of the nutrients to the liver. And the cool thing about the hormones going straight to the liver first means that the effects they have there are four times greater than what you will see in the rest of the body. So insulin and glucagon from the pancreas will have four times greater effect in the liver than in the rest of the body. But now the thing about the pancreas is that it doesn't just contain insulin and glucagon hanging out in random cells, they're organized. So if we blow up a small part of the pancreas right over here, we would see this. Which is a collection of cells here, like an island, surrounded by other cells. These other cells on the outside secrete enzymes that go into the GI tract, and we won't worry too much about them now, but the cells here in this island are referred to as the islet of langerhans. So it's the islet of langerhans. Which is just a fancy term for an island of cells. And the way the cells are organized in here is very structured. You'll have what are called beta cells in the middle of the island and on the outside you'll have what are called alpha cells. So alpha cells on the outside. And the key thing to remember here is that your beta cells release insulin while the alpha cells release glucagon. The alpha cells release glucagon. And we can actually go into further detail about how beta cells, for instance, secrete insulin into the blood. Let's start by focusing on this beta cell right here. I'll be sure to label this. This is a beta cell right here. This is our beta cell and these guys store insulin. So I'll write insulin here in this secretory vesicle. And I'll show you how it's released into the blood stream. This secretory vesicle, much like many secretory vesicles in the body, will release their contents outside of the cell if there's calcium present. So I'll put this calcium receptor here for now. The other thing that's unique about beta cells is that they have these potassium channels. So potassium channels that allow potassium to leave beta cells through facilitated diffusion. So they're just naturally leaving the beta cell over time. Which means that at rest there's a lot more potassium ions living outside of the beta cell than there are inside of the beta cell. And that's an important distinction because that's how we prevent the beta cell from being depolarized or getting a more positive charge within the cell. And this potassium channel also has a receptor on it, that I promise I'll go into more detail about in a minute. But it grabs onto ATP, the basic molecule of energy. And in addition to the potassium channel, there's also this calcium channel. So it's a calcium channel that's sitting here like in most cells and open through depolarization. And we'll go into how that happens in a second. All right, so now we're ready. How does insulin leave the beta cell? Well the first thing that has to happen is that glucose needs to enter the cell somehow, because when there's a lot of glucose around we wanna store it away. That's what insulin's supposed to do. And the way it enters is through this unique transporter. It's called the glut 2 transporter. And it allow glucose to enter into your beta cell. Once we get glucose inside of the cell, glucose will undergo what it usually does in most cells, processes such as glycolysis or be broken down into things that are sent through the krebs cycle. And doing this second thing here will produce a lot of ATP molecules. We mentioned ATP already. ATP is that basic form of energy. And it's important in this cell, because once we start to build up the amount of ATP that's present, some of it will go down here to this potassium channel and bind the ATP receptor that sits here. Now the interesting thing about this ATP receptor is that once it locks in, it'll actually block off this channel. It'll prevent potassium from leaving, so the next thing that'll happen is that the amount of potassium in the cell will start to skyrocket because there's no way for it to get out anymore. So you'll have a lot more potassium, or a lot more positive charge inside of the cell, than you have relative to what's outside. And what that's going to do is cause depolarization, depolarization of the membrane of the beta cell. That then will go and activate these voltage gated calcium channels, allowing calcium to enter the beta cell, which in turn can also cause calcium dependent calcium release into the cell. But overall it starts increasing the amount of calcium that's present on the inside. And as you might remember, the insulin secretory vesicle has a calcium receptor here. So sure enough, the next thing that occurs is that calcium will bind this receptor, causing this vesicle to fuse with the membrane of the beta cell. That'll cause insulin to be kicked out of the beta cell and be released into the blood stream. This step here, as you might recall, this final step that kicks the insulin out of the cell, is what's called exocytosis. Exocytosis, where a vesicle fuses with the cell membrane to release it's contents into the outside, or the extracellular space. Which in this case, is the portal venous blood, which will send it to the liver. So that's how insulin is released from beta cells. What about glucagon? How is it released from alpha cells? Well, unfortunately we don't know as well how this process works. All we know so far is that amino acids trigger glucagon release. How it does this specifically is a question and even perhaps a Nobel Prize up for grabs, which I think is fair to say, because the Nobel Prize in 1923 went to two scientists named Banting and Best for discovering insulin. And the crazy thing about that is that Charles Best, who shares in the Nobel Prize was a medical student the time the study was done in 1921. And then two years later, he was able to share the Nobel Prize with his professor, which is just mind boggling to think about.