BIO2 week 4b part 2

hyoerglycemia

HYPOGLYCEMIC: Glycogen to glucose HYPERGLYCEMIC: Glucose to glycogen

insulin and glucose in different cell types

insulin lowers blood glucose by opening GLUT 4 channels

insulin binding open sglut4 channels on any cell (if liver, some glucose enters and converts into glycogen) (if other, glucose enters and is used for cellular respiration)

NUMBERED STEPS TO insulin REACTION

1) INSULIN BINDS TO EXTRACELLULAR RECEPTOR, CHANGING ITS SHAPE

(receptor on the outside because its peptide so polar, but it stillis connect to transmembrane protein)

2) PHOSPHORYLATION OF INTRACELLULAR PORTION OF RECEPTOR

phosphoralation: a bunch of phosphate groups attatched to the iinternal part of transmembrane protein because of a signal given

3) chemical cascade

this is all to move a vesicle (storage unit inside of cells, similarly to bubbles) which is made of a phospholipid membrane and a GLUT4 transporter (transmembrane protein that will let ___ flow through it)

the vesicle will move into MEMBRANE away from cytoplasm

4) moves GLUT-4 transporter vesicle to the plasma membrane 5) glucose channels opened and glucose enters cell

these are passive: CALLED CHANNEL AND NOT PUMP

6_ insulin breaks down and GLUT4 turns back into a vesicle (channels close)

Signal transduction (Wikipedia definition)

Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events. Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term sensor is used. The changes elicited by ligand binding (or signal sensing) in a receptor give rise to a biochemical cascade, which is a chain of biochemical events known as a signaling pathway. When signaling pathways interact with one another they form networks, which allow cellular responses to be coordinated, often by combinatorial signaling events. At the molecular level, such responses include changes in the transcription or translation of genes, and post-translational and conformational changes in proteins, as well as changes in their location. These molecular events are the basic mechanisms controlling cell growth, proliferation, metabolism and many other processes. In multicellular organisms, signal transduction pathways regulate cell communication in a wide variety of ways. Each component (or node) of a signaling pathway is classified according to the role it plays with respect to the initial stimulus. Ligands are termed first messengers, while receptors are the signal transducers, which then activate primary effectors. Such effectors are typically proteins and are often linked to second messengers, which can activate secondary effectors, and so on. Depending on the efficiency of the nodes, a signal can be amplified (a concept known as signal gain), so that one signaling molecule can generate a response involving hundreds to millions of molecules. As with other signals, the transduction of biological signals is characterised by delay, noise, signal feedback and feedforward and interference, which can range from negligible to pathological. With the advent of computational biology, the analysis of signaling pathways and networks has become an essential tool to understand cellular functions and disease, including signaling rewiring mechanisms underlying responses to acquired drug resistance.

transport- movement of MOLECULES into cell across a membrane

shape of transport protein dictates what can pass through it

transduction- passing of a message/signal across a membrane

insulin does not exactly enter a cell, but instead sends its signals through a cell membrane.

GLUCOSE is transported into cell for this

this isi nly ONE o the effects of insulin signaling out of many

what's diabetes

identified by elevated blood glucose

the glucose itself isn't the problem, but they aren't where they need to be

WAYS GLUCOSE TRANSPORT DOESNT WORK

insulin mutation

liver not capable of converting glucose into glycogen

shape of insulin isn't right

hypothalamus receptors not working and not correctly monitoring signals

phosphorylation error, chemical cascade error, not enough of it

TYPE DIABETES

TYPE 1: PANCREAS NOT MAKING INSULIN no insulin means no bond means no transport. this is a product to an autoimmune disorder TYPE 2: receptor problem. receptors become desensitized and isn't binding well or no real response when it does bind, unknownish. INSULIN ABILITY TO RESPOND. INSULIN RESISTANCE CONTRIBUTES TO HIGH GLUCOSE LEVELS IN BLOOD

Check for insulin levels, by extracting their blood, so if they have lots of insulin they have type II and no insulin is Type 1. Give insulin and blood sugar drops, type 1, other type 2

look for pancreatic cells ia xtration

BIO2 week 4b part 2

Transcript

Take a couple minutes and talk through the process of digestion, monomer transport, elevated blood sugar, but then add on the piece about endocrine regulation.

So talk about that for a few minutes. See if you can include as many details as you can, and then you can go on and answer question one as review before we get going, and then we'll stop, talk through it, and do announcements.

So give yourselves a couple minutes. Talk through the process in as much detail as you can.

You ever seen. Oh, okay. It converts what into? I'm going to say glucose. Both of these are glucose. One of these would be glycogen. Because I want to say glucagon is just. It's not something it converts to, but it is a. I'm very proud of my girls. We were like. We gave you time to, like, quickly, like, your fit today.

I like your fit today. I would start doing that, but my con is kind of ass.

I need to be. I want to get a new one, but not here. I want to get it when I go back home. All right, so let's talk through the system. How did you feel? How confident were you about the endocrine part?

Okay, so hopefully you talked about the part where you just ate and your blood sugar is high.

So you've talked through the, like, part of the pathway that deals with hyperglycemia.

We'll talk about that in a second, but I'll talk through the part, at least the endocrine part with hypoglycemia.

So instead of having just eaten something really sweet, if it hasn't been a while since you ate anything and your blood sugar starts to drop, one solution to that would be to eat something if that breaks down into glucose.

But if that's not an option and you're hypoglycemic, then the low amount of blood sugar is going to be monitored by your hypothalamus, which is a piece of your brain.

So your brain, which is constantly monitoring blood sugar, is sending reports to the control center, which is the pancreas.

The pancreas, upon receiving this report from the hypothalamus that your blood sugar is low, is going to respond by releasing.

What if your blood sugar's low, what is your pancreas gonna make?

Glucagon. Glucagon. Glucagon is the hormone that your pancreas makes.

So glucagon is released by the pancreatic cells.

It's gonna enter the bloodstream. Glucagon is a protein. It is going to dissolve in the blood because it's polar.

So it's gonna travel through the bloodstream and it's gonna travel all over our body.

So it bumps into an extracellular receptor in its target locations.

So the target location for glucagon is in the liver.

So when glucagon binds to liver cells, it's going to undergo signal transduction.

So it's going to send a message into all those liver cells that it should do something.

And the thing that the liver cells are going to do in response is to take glycogen, this polysaccharide polymer of glucose molecules, and start to break those glucose molecules down back into.

Or, sorry, break down the glycogen into glucose.

That glucose is then going to be put into the bloodstream.

But because glucose is polar, it can't just, like, diffuse through the cell membrane.

So it's gonna need a transmembrane protein in order to exit those liver cells back into the bloodstream.

Where, again, because it's polar, those glucose molecules can just dissolve in the blood and move around, raising blood sugar back to within a normal level.

Okay, how'd that go? Yeah. Okay, so as far as the little question goes, it was.

The version I just told was the hypoglycemia version.

Right. So in hypoglycemia, when our blood sugar is low, what's happening in the liver is we're converting what to what.

What is getting converted when we're hypoglycemic?

Glucogen Gone to glucose. Glycogen to glucose. Right. Glucagon shouldn't actually be an answer in any of your things.

Glucagon is a hormone that is created by the pancreas and binds to the.

To the liver cells itself. It doesn't get broken down, so the glycogen is going to get broken down into the glucose.

When we're hypoglycemic, if we're hyperglycemic, if we have too much blood sugar, what's the.

I said, what's the insulin? What's the hormone that's going to be produced by the pancreas?

Insulin is going to get produced. It's going to signal the liver to convert that excess glucose into glycogen in order to store it.

So it's either glycogen to glucose or glucose to glycogen in one of those two circumstances.

Questions about that. All right, so what we're going to do today in just a second is kind of continue that story.

So we've talked about how the release of glucose brings.

Sorry, the release of insulin brings glucose into cells.

We're going to talk about the cellular process that actually is happening in order for that to work.

Before we get to that, just a couple of announcements, two things, maybe three things.

So when we get back from break, there is going to be a research night in the plant biology department.

So a lot of you have been asking about research opportunities lately.

And so I want to take a minute just to like say some broad things about research.

It is getting into a research lab is always going to suck.

It's really hard, it's annoying, it takes a long time and it's really frustrating.

I don't know of a way around that exactly. So what you can do is like limit the pain by enhancing your opportunities to meet face to face with people who might be able to have space in their lab and then like start to build those networks.

Now one of the ways to do that is to attend like meet and greet events like this.

So this one's in plant biology. I hear about this one because that's my department.

I am almost positive these kinds of activities happen in most of the biology departments on campus.

So whether it's marine sciences or biochemistry or entomology, all of them have student organizations that put these kinds of events on.

They're just really hard to hear about if you're not already plugged in.

So one of the things I would always suggest doing is even if you're not like a major in a department like this, get involved in one of these departments that interests you.

Get on their listservs, get a part of their like organization, like emails.

By getting a lot of those, you're going to increase your opportunity to like actually talk to someone at this event on the 5th.

On the 5th there are going to be a bunch of faculty there.

Not all of them are going to have spots in their labs where they're looking to fill graduate students, but they are there to talk to about like what are you looking for when you get an email from a student looking into your lab?

How do you suggest kind of going about that process?

What are some of the things you're looking for in terms of qualifications?

Or like there's a lot that can be gained by talking to people and the more people you can talk to, the better your chances are of actually like having this be a fairly pain free process.

So again, increasing your opportunities to see people, to meet people is always good.

Organizations are good, these things are good. They're just really hard to find. And I don't Know why that is and why there's not like a better central process with the biology division, but there just hasn't been so far.

Anyway, happy to talk individually about like your research interests and trying to point you in the right direction, but this is a really good, like, idea if you really don't know or if you're like trying to figure it out.

The other thing is, like, plant biology, you're probably going to be working on like plant cells or plants, but that doesn't mean that's what you want to like necessarily do forever.

I've mentioned this before, but in the plant biology department there are people doing genetics and cell biology and physics and like biophysics and ecology and like remote sensing.

All different kinds of fields are represented in a lot of these departments.

So don't feel hemmed in. Like, if you want to do cell biology, there are cell biologists all over campus.

If you're looking to go to med school, they don't care whether you have experience doing cell biology research on plant cells or mouse cells or human cells or like Drosophila cells, it's not going to matter.

So getting the skills is what matters. So keep that in mind when these kind of opportunities cross your paths.

Okay, that's my little research spiel. Other than that, just a couple of other announcements.

I will post the weekly review quiz today. It will be due on Monday, along with the like 10 minute little symbiote graphic thing.

So if you haven't done that, make sure you do that by Monday as well.

Yes. Is that the same? There's two of them. This is the second one. So there's that one. The other thing is, I am not going to have office hours tomorrow.

So I had office hours today, you guys. I didn't get to tell you that. But no office hours tomorrow. I'll have regular office hours next week along with all the exam reviews.

So I will post like a specific schedule for the next Wednesday to look at your exam with times and places.

The exam debrief is going to be next Tuesday. Exam reviews will be on Wednesday. Questions about any of that? Yes. When can we expect the extra credit tomorrow? Extra credit has already been sent out. It was as an announcement. Was that right? I think you should have gotten an announcement. Check the announcements. It's worth 10 if you do all of the sections. Okay, then let's keep going. Let's talk about extra credit after, if you don't mind.

Okay, so just as a very quick review from last time we talked about what's going to be the endocrine response to elevated blood sugar or low blood sugar.

So in terms of low blood sugar, if our blood sugar drops too low, the first thing that's going to be affected is the hypothalamus, which is monitoring the concentration of sugar in our blood.

It's going to send a signal to the pancreas, our control center, that's going to then have to make decisions about what to do.

The pancreas, in this case, is going to make glucagon, this hormone that is a messenger molecule that will travel through the bloodstream until it hits receptors in the liver, at which point it will induce the liver to start converting, converting glycogen into glucose, which releases into the bloodstream, raising our blood sugar back to within normal levels.

On the other side, if we instead we just had something really sweet and we've digested it and it's entered our bloodstream and our blood sugar spikes, the receptor again, hypothalamus sends that information to the pancreas.

But this time, instead of sending glucagon, it's going to release insulin.

And when it does that, insulin travels to a bunch of different places and effectively lowers blood sugar.

Now, what we're going to do. So hopefully that was like a very quick review. What we're going to do today is think about what's happening as insulin binds to cells.

And just as a little bit of like a diagram, visual model recap, we're going to talk about something called GLUT4 today.

Glute4 channels are transmembrane proteins that allow glucose to pass through them.

So we'll talk a lot about glucore channels in a second.

Now, when those glen and glucose comes into cells, there's like two options, right?

So insulin binds the cells receptors, extracellular receptors.

Again, we're going to talk about what's going on in this box in a minute.

But when GLUT4 opens in liver cells, the glucose that enters is going to be for storage.

So the glucose that enters liver cells is going to be stored, and it's a pretty small fraction of the total blood glucose that's going to kind of go down through the sludge.

If Insulin instead opens glute 4 channels on other cells, fat cells, muscle cells, in that case, which is most of the cells in our body that respond to insulin, in that case, that glucose is going to be used for cellular respiration.

So I just want to, like, differentiate between these two different uses for glucose or the two different things that happen to glucose once they enter cells in the liver, they're going to be stor everywhere else, they're going to get broken down and used through cellular respiration for ATVs.

Okay, so let's talk about how on a cellular level, insulin allows glucose to enter cells.

That's kind of a black box at the moment. We've talked about how that happens. Insulin, when it's present in the blood, binds to receptors and glucose levels in the blood go down.

So we're going to talk specifically about the sequence of events that allows this to happen.

To do that, I'm going to use this little diagram with numbered steps.

These numbered steps, kind of like the light reactions, are snapshots of this whole process.

Ultimately, you're going to want to view this process in your head as like a movie, just like low light reactions, it's kind of a continuous event.

But for now, we'll just talk about these snapshots.

Now, to begin this process of glucose transport into cells, the first thing that's going to happen is that insulin that's already present in our bloodstream because we have already eaten and there's lots of glucose in our blood, and our pancreas has responded to messages from our hypothalamus.

When there's lots of insulin in our bloodstream, which is going to be these little purple triangles, the first thing that's going to happen is that that insulin binds to that extracellular receptor.

We know it's going to be an extracellular receptor because insulin is a protein or a peptide hormone.

It's pulled so its receptors on the outside of cells, but it's connected to this big transmembrane protein.

So when insulin binds, that protein changes shape slightly.

We call it activated. So when insulin binds, it's going to activate that protein by changing its shape, similarly to the way like an induced fit enzyme changes shape when it binds.

Same idea here. So that's number one. Now, when that receptor changes shape, when that transport or the transmembrane protein changes shape, the first thing to happen inside of the cell is that the interior part of that transmembrane protein becomes what we call phosphorylated.

So phosphorylation is the first. Now, phosphorylation is a really common like reaction that happens in a lot of biochemical processes.

Phosphorylation just means, as you can kind of see here, a bunch of like, phosphate groups just attached to the inner part of this transmembrane protein.

So that's what's going to happen first. This change of shape means all these Little phosphate groups attach to the internal part of this transmembrane protein because they've gotten a signal that insulin is bound externally.

Now, that phosphorylation is what I like to think about as, like, the first domino in a sequence of events that's about to happen.

So it's the first domino to fall that's going to kick off this chain reaction of chemical reactions that's really long and complicated and honestly, not our problem.

When you take biochemistry, you're going to learn all about it.

But for us, we're just going to call everything that happens afterward a chemical cascade.

And we're going to, like, hand wave it away with this creepy blue hand.

So we just get to, like, call everything that happens next a chemical cascade.

It's just a sequence of things that are going to happen.

But the goal of that chemical cascade is to move something called a vesicle.

So a vesicle. We haven't really talked about vesicles. Vesicles are kind of analogous to a vacuole. It's a storage small. It's like a storage thing inside of cells. So right here we have what we call a GLUT4vesicle.

Vesicles are like bubbles that can store stuff inside.

But that's not actually what this vesicle does. This vesicle is a bubble of phospholipid membrane.

So it's made of the same stuff as a regular cell membrane.

It's a phospholipid bilayer, and it forms this, like, bubble.

But embedded in the phospholipid membrane of this vesicle is something called a GLUT4 transporter.

So a GLUT4 transporter is a transmembrane protein that eventually will allow glucose to flow through it.

At the moment, that vesicle and that GLUT4 transporter are stuck inside the cell, they're not on the external membrane.

So what this chemical cascade's job is, is to move this vesicle into the outer membrane.

And when it does, it acts like a soap bubble. Like two soap bubbles, like, popping together. They kind of, like, merge. So that chemical cascade is going to move this glut4vesicle and kind of pop into place.

When that happens, that gluc4transort protein is no longer stuck inside the cell.

Instead, it now spans the width of the outer membrane instead.

So the GLUT4 transporter, once it reaches that outer membrane, it's going to be open and it's going to allow glucose to.

To flow through it. Into the cell. Is this going to allow for the transport of glucose through active or passive transport?

Passive. Passive. How do we know it is passive transport? Because it's not using energy. I think that's two ways, right? We just ate. There's lots of glucose around, which is why there's insulin around in the first place.

So there's lots of glucose around. So there's a high concentration outside the cell.

But also it's called a channel and not a what? Pump. A pump. If this were a pump, we would know it's active transport because this is not a glucose pump.

It has got to be passive transport. So glucose can only flow through GLUT4. Through passive transport, it has to flow from high to low.

All right, so now we're here. That little Glut4pur protein is stuck inside the cell membrane.

Instead, glucose is flowing into the cell according to diffusion.

And this will happen as long as that glut 4 is embedded in that outer membrane.

But eventually, what's going to happen is that this glucose, or, sorry, the insulin, starts to break down.

Enzymes start to break it apart. It starts to degrade. For one reason or another, that insulin is going to disassociate from its receptor.

When it does that, this whole process kind of moves in reverse, and that glute 4 transporter is reformed into a vesicle.

So as insulin breaks down, that glut 4 channel is removed from the membrane and reformed as a vessel.

At this point, then glucose is stuck where it is. There's no way for it to move across the membrane unless it has a gluten transformer.

All right, so I want to show you a quick video. It doesn't have all the details, but it's got enough.

So let's. I turn the volume off because it's kind of weird, but.

Okay, so we're going to start. Okay, so where we're starting is we have this yellow insulin molecule.

Here's our transmembrane protein. That includes the extracellular receptor for insulin.

So when insulin binds, it activates that receptor, it changes the shape of it.

And ultimately, what's happening here inside the cell.

Phosphorus. That phosphorylation. Right. So that's the beginning of a chemical cascade. That, again, is not our problem. That is biochemistry's problem, which you'll talk about all of those steps in biochemistry.

You can look forward to that, but not our problem.

So when that chemical cascade is happening, it's forcing this little vesicle that contains the GLUT4 transport protein, pour the outer Membrane where it will kind of pop into place.

Once that glut 4 is in the outer membrane, glucose is going to be allowed to pass through with passive transport.

Once insulin starts to degrade, enzymes are breaking it down.

It's going to disassociate from its receptor. When it does that again, that vesicle is going to start to reform.

It's going to wait for the next time that we have elevated blood glucose and insulins around and binds to receptors.

So it'll stay inside the cell until that next round of high blood sugar.

Okay, so here's your assignment. No, not that. Oh, wait. Yes, this. Okay, so taking a look with the people near you, try to talk through this process.

Try not to use your notes. You can still use the picture, but see if you can talk through the process and then think about why this happens.

Once you do that, you can go on to question two on your.

So basically I forgot the meaning of trans. Illustrating trans. So basically insulin sends the signals, sorry, can be made or whatever, and group four then puts itself in the membrane so that glucose can come into the cells.

And that's why, I guess, no, I literally couldn't feel like such a messy sleeper and I didn't want to say that to him.

But like, you know, literally like randomly kicking rapidly anyways, so the inside it binds their shape and they interior part becomes phosphorylated.

Then we begin a chemical cascade that pushes the glute poor containing vesicle to the outer membrane.

Yeah, I don't know what transduction. I think transection is just the process of the insulin.

Like this whole glucose comes in through. So essentially we have glucose and we have our insulin receptors.

Insulin receptors then inserted into the receptor which channels the receptor, the containing vesicle to move upwards.

As it moves upwards, that movement channels the Group 4 channel to be open, giving glucose the chance to have passive transport down and to the cytoplasm.

And then once the insulin breaks down and the receptors can no longer use it, it lets go and stops that process.

Blue force slowly returns back and the channel closes.

She did say wave away like two to three. That little section right there. Receptor send signals, Route 4 goes in into the membrane so that glucose.

I feel that maybe. How is that transduction though? I don't know. What did it say? The definition of signal transduction is the process by which a chemical physical signal is transmitted through a cell as a series of molecular events.

Well, that's what, that's what it's doing. That's exactly what it is. I spend very much time talking about transactions, so we'll talk about that in just a second.

But first of all, let's think about why and when this process happens.

Like, it would seem way easier just to always have glute transporters in our cell membrane.

Why go through this whole process of, like, signaling and moving vesicles around and only opening channels in certain circumstances?

Resources, energy. Why do we think we just don't have open glucose channels all the time?

Cells that might need it, so we always have some glucose in the blood.

I think that's kind of where I land on this, is that if we had open glucose channels all the time, it would be possible, if our glucose levels dropped pretty low for our really important cells, the cells in our brain, our neurons, it would be possible that they might not have access to glucose when they really need it, while other cells that are kind of expendable or, like, can be tired and it doesn't matter as much, we're putting those really important cells at risk.

So by having this system of they're only allowing glucose into muscle cells and fat cel cells for storage.

If we only do that when we have a lot of glucose around, it kind of buffers things like neurons.

So when we're going to talk about neurons, next unit, they use a tremendous amount of energy.

So if our glucose levels drop too low in our blood, they're the ones that are really going to feel it most, and we're going to be in big trouble if they don't have enough glucose.

So it's a way of, like, dealing with that. That's kind of excessive in terms of stuff we need to talk about, but I think it's kind of interesting to think about.

Okay, so transduction versus transport. In this system where we have this insulin coming in, is insulin itself entering the cell at any point?

No. Instead, insulin would be what we're kind of calling.

Oh, I did. The other way around. Okay. So transport refers to things where molecules move into a cell.

So insulin is not doing transport. It's not actually entering the cells. What is being transported? Glucose. Glucose is being transported. Insulin is not. So transport is the movement of a molecule, and we know that it's got to be.

If we're talking about polar things, it's going to use transport proteins that are specific to a certain thing.

So glucophore transporters only allow glucose, nothing else.

Transduction instead is the passing of a message across the membrane.

Insulin is doing that. So it's not actually entering the cell, but it is able to undergo transduction.

So signal transduction is what insulin is doing.

So it's sending a message without actually entering some message.

So things that do this are hormones. We'll talk about neurotransmitters as being very similar to hormones in a lot of ways.

Next unit. Okay. Now learning about this process of insulin's job in transporting glucose, I guess I want to do a little bit of a disclaimer.

That is one impact of insulin. Insulin is actually linked to an incredible array of processes and signaling pathways in our cells that don't just move glute four, transport vesicles around, but do all kinds of other things, too.

We're only worried about the one impact of insulin that we've.

So don't worry about everything else. If you're running across stuff, that's certainly true.

We're just going to kind of narrow our focus in terms of insulin.

All right, so we've got all these different things happening with insulin, but focusing on that glucose portion.

Let's talk about diabetes. So in terms of diabetes, we talked a little bit about this before.

We know that diabetes is kind of identified by this high level of blood glucose, but we also talked about why it's bad to have high blood glucose.

Is it the glucose molecules themselves in our bloodstream that are causing the issue?

No. What's the problem? The place, the setting? Yeah. They're not getting to where they need to be. Right. So if they're stuck in the blood, like, we're always going to have elevated blood sugar after we eat something.

But if it's like that for too long, it means that glucose is not getting to where it needs to be.

And now we know something about the mechanism, about how that works, how we actually transform that glucose.

So if we have elevated blood glucose for too long, there's a problem.

Because there's a problem with that last mechanism we talked about.

Somehow the glucose is not getting into the cells.

Now, there are two real types of diabetes that have specific causes.

But if we think about all the stuff we know so far about glucoregulation, there are so many different ways that we could wind up having elevated levels of blood glucose.

What I want you to do in the next couple minutes is talk to the people around you and come up with all the different ways you can think of that we might wind up with high levels of blood glucose.

Think about what's going on on a cellular level today.

Think about what's going on with our endocrine system.

Think about what's going on to get Glucose into the blood in the first place, digestion, the signaling mechanisms that we're using, all of those pieces could be important here.

And a breakdown in lots of different places could result in elevated blood sugar.

I want you to try to come up with three, and they do not need to be real, like ways that the diabetes happens, but come up with three ways that you can imagine us winding up with high blood sugar.

See what you can get. So the first one would obviously be eating too much sugar that your body doesn't have a chance to predict reduce them.

Second thing would be if we're talking about hyperglycemia, the way that that glute four moves up somehow the insulin, maybe the insulin doesn't have a chance to always hit that insulin receptor when there's blood glucose to be converted.

Or maybe the insulin, when reception isn't like, like working properly, then the vehicles can't get in to the.

Oh, we're talking about too much. Okay, so somehow the channels aren't. Somehow the channels are not close. Something's wrong with the channels and there aren't Cl.

The vesicle is stopped and can't move from out of the side.

Class maybe. Or were you going to say. I say that the insulin must have, I don't know, somehow sends too many signals and too many glute for, like things get put into the membranes.

Yeah. Too much insulin. Yeah. And then too much glucose gets into ourselves. What's the other one? Maybe something with glucagon, too. I don't know. I'm going to say with glucagon. Oh, hi. Hello. Oh, is this one of the questions? Yeah, yeah. Okay. Your liver convert. I was thinking maybe. Well, your liver could not convert. Convert glucose into glycogen. How? Earlier there was like a receptor that takes up the insulin, so it sends like a signal down.

It's just. Insulin receptor. Yeah, yeah. If your body got exposed to like something like, I don't know, radiation, that could destroy the insulin receptors.

I was also thinking, I don't know if there is a case, but the glute 4 vesicle gets stuck by the membrane and doesn't go back into the cytoplasm when that function is finished.

So that channel is constantly open for glucose to enter.

That was me drinking all that Dr. Pepper. Me drinking all that Dr. Cooker on Monday and waking up to heartburn. Dude, I have insane heartburn. I didn't give you guys as long as I usually do, but let's hear some of your reasons.

I saw actually a pretty good Range of possibilities here.

So what are some of the things that might result in high levels of blood glucose?

What do you come up with? What do you got? Insulin receptors don't work. Why would they not work? These are made of proteins. We know that proteins rely on a genetic code to, like, code for their structure and their folding.

So if there's a mutation in those, that works. Yeah. Yeah. Or if we have elevated glucose, then maybe the other way around.

Right. So maybe our liver is not capable of, like, converting glucose into glycogen.

So the liver. Or, like, I don't know, there's like, excess. The glucose isn't entering liver cells and gets stuck in the.

In the blood. Sure. What else? Yeah. Also a protein. Right. So maybe the shape of insulin isn't right. If the insulin isn't right, it's not going to bind to the receptor.

If that's not right, then this whole process of moving those GLUT4 transporters into the cell membrane isn't going to function.

Yeah, maybe the hypothalamus, like, receptors aren't working.

Yeah, let's go further back. Maybe there's a problem with the hypothalamus. It's not correctly monitoring blood sugar. It's sending bad signals or it's not picking up signals.

What else? So something with phosphorylation. Maybe there's not enough phosphate around. Maybe you guys back there got the fact that maybe there's something wrong with the chemical cascade itself.

Any one of those little chemical reactions in that chemical cascade, if it breaks down, means that that glucore is never going to make it into the outer membrane.

Glucose is never going to get transported into cells.

Those are pretty good. There's lots more that you guys could have chosen.

It's one of those things. And we'll run into these again. It's, like, incredible that it ever works, that so many things have to go right in, so many pieces have to fit together exactly in the right way that it's amazing these processes ever function the way that they're supposed to.

Okay, so when we're thinking about actual diabetes, there are two of those ways that you mentioned that we see as type 1 or type 2 diabetes.

So let's talk about those. We know that they both result in elevated blood glucose.

The difference being that in type 1 diabetes, it's that your pancreas isn't making enough insulin or isn't making good insulin, or basically it's not making insulin.

We'll talk about why in a second. So type one is an insulin Problem. Okay, so type one is a problem with the pancreas. The problem is that it's not making insulin. I'll come back to this in a second. But if you're not making insulin, that means that insulin can't bind to those receptors on all of our cells.

It can't allow that glucose transporter to enter into the cell, and glucose can't flow in.

So basically, type one is this inability to produce insulin.

We'll talk about this more later. But this is actually a product of an autoimmune disorder.

So type 1 diabetes is usually considered an autoimmune disorder.

The reason that a type 1 diabetic can't make insulin is because in any autoimmune disorder, it's like your.

Your immune system attacks the wrong thing. So in type 1 diabetes, their immune system is attacking the cells in your pancreas that make insulin.

So they're called beta cells. We don't really have to know that. But type 1 diabetics, their immune system attacks beta cells, which means they can't produce insulin as a consequence.

Okay, so that's type one. Type two is not a problem with the pancreas. The pancreas seems to function fine in type 2 diabetes.

The problem is on the other end. The problem is with the receptors. So what we say about type 2 diabetes is that the receptors themselves become desensitized.

Physically, they're still there, but insulin, like, isn't binding well, or when it binds, there isn't a real response.

And there is a whole lot we still don't know about that process.

So by calling it desensitized, we're kind of watching over the fact that we don't know exactly what mechanism is leading to this.

But Basically, in type 2, this is an inability to respond to insulin.

It's not an insulin problem. It's ability to respond to insulin. This is a problem. Okay, so if these problems. Let's think about these are obviously very different causes.

Right. They have the same eventual impact. So what would you do if you were in a doctor's office and someone walked in and had really high levels of blood glucose?

I want you to try to think of ways that you might be able to diagnose them as having either type 1 or type 2 diabetes.

How could you figure out which one they have? See if you can come up with one or two ways. I will say this only has to work. It does not have to be ethical. Wow. Just check their insulin levels. If they have too much, if they don't have a lot of insulin, then obviously they have type one because their pancreas isn't producing enough.

And if they have insulin present, then it's just not, like, you know, working correct.

How would you check for it, though? I don't know. I don't want to get into details. Humane detail. That's what she wants. We got to figure them food, then monitor their intimate.

You may need more than just so really too little insulin would be type 1 and then insulin there.

But, like, it's not reducing the amount. Yeah, glucose, then that's obviously type two. It doesn't seem biggie. It would just take a few hours to reach. What's another way I can do this? I would attempt to diagnose them by blank. This is the same as writing B for essay. What have we got? What are some things we might want to try to figure out if someone has typed 1 or type 2 diabetes?

What do you got? Yeah, we can look for insulin, Right? So if someone has lots of insulin around, what kind of diabetes do they have?

Type 2. They have type 2 if they don't have insulin, that'll tell you they got type one.

Great. That's a diagnostic test. We can do that. What else could you do? Yeah, pump them full of insulin and see what happens.

Wow. So if you give them a big shot of insulin and their blood sugar plummets, what do they have?

Type 1. Type 1. If you give them insulin and their blood sugar drops, then they were just missing the insulin.

Everything else works. Right? So if you give them insulin and the blood sugar drops, type one, if you give them the insulin, nothing happens.

That's when it got tattooed. All right, now we get into the more questionable things.

Pop them full of sugar and see what happens. So, all right, so if you pump them full of sugar and their sugar level rises, what do you think?

Ah, if their insulin level rises. Yeah. Okay, good. Oh, boy. Harvest cells from their pancreas. That is dross Blood blood cells that attack. We can look for antibodies in their blood that otherwise attack pancreatic cells.

Anybody else have something? No, wait. I'm sorry. Okay, the answer is 1, 2, 1. Let me see. I can't hear you at all. Okay, so that's it. If you submit, we will see you on 2 Monday. See you on Monday. That's 2, right? Hold on. Hypoglycemic is 2. Hyperglycemic. The first one is 1. I am too. I did the practice exam, got a 92. But, like, the practice exam is never the same. Like the exam review. Exactly. We did everything, except I didn't do recitation line because the way I looked at it, and I was like, okay.

I hope so. I, like, saw him. I was like, yeah, well, okay. Like, no, thanks. All right. Okay. Good luck on it. Thank you, too. How'd you guys do on the bio? I'm taking SD6. Oh, I got a 84. 84 type. I got an 88 type type. What did you get? I don't feel comfortable sharing it with you. Kidding about it. I am going to yack about it. It's not 100. I got a 96. Thank. In a good mental state. Last week. No, last week is crazy. Last night I did cry. I wish I could.