Exercise Physiology | Hormonal Control of Fuel Sources (Part 4)
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applies to online activations, requires port in and auto pay. Customers activating in stores may be charged non-refundable activation fees. Welcome everybody to another episode of Dr. Matt and Dr. Mike's Medical Podcast. I'm your host, Dr. Mike Todorovic, and I'm joined by my co-host, 1960s Batman, Adam West. How are you, Adam? I went to the doctor the other day.

And during the examination, I said to the doctor, what do you think it is? And he said, look, I think mercury is in your anus. And I said, look, look, doc, I'm not into that astrology crap. He said, nor am I. My thermometer broke.

Very nice. When the moon is in the seventh house and Jupiter aligns with Mars. Do you know that song? And peace will guide the planet.

This is the dawning of the age of Aquarius. The age of Aquarius. Nice. Okay. That's from my favorite musical, Hair. Okay. There you go. How are you? How are you? Are you good?

We're deteriorating as podcasters. We are, and as human beings, I think, as well. Hey, did you know that on Saturday the 29th of March, I will be part of World Science Festival, and I am at the concert hall at South Bank, which is the big hall there, presenting a great debate, a scientific debate,

I don't know if I can say what the actual debate topic is. I don't think I'm allowed to say what it is.

Let's just say I'm on the negative, so I've got to argue against the topic, and I think I'm going to do a pretty good job. Tickets are still available. Go to worldsciencefestival.com. Book a ticket for the Science Smackdown, the great debate, I believe it's called, or the ultimate debate. I will be there. For those Australians of a similar vintage to myself, Ranger Stacey is on my team.

from Agro's Cartoon Connection. I don't think our international listeners will know what that is. Feel free to Google, go onto YouTube and type in Agro's Cartoon Connection. It was odd, but it was cool. And I'll be doing that, Matt. So that's going to be enjoyable. Let's hope this podcast is released before that. I think it will be. I think I'm going to be releasing this podcast episode within the next couple of days. And today we are continuing Agro's

journey through exercise physiology. And specifically what we're focusing on today is basically how we use hormones during exercise. So we know, we spoke in the last episode that there's different fuel sources that we utilize, proteins, fats, and carbs. We utilize them differently depending on the intensity of the exercise. But what regulates us utilizing each of those fuel sources, a big part of that is hormones. How does the muscle know?

Yeah. How does the muscle know? Because of the hormones. So we're going to talk about a range of hormones covering growth hormone, cortisol, thyroid hormone, adrenaline, insulin, glucagon. So there's a whole range. But before we get there, my dear friend, Matthew-

friend, I said. We need to discuss what hormones are. Now, the listeners are probably going, we know what hormones are. I get it. These are chemicals released into the bloodstream. They have effect on tissues. You are correct, but there's more to that. And we need to get some concepts down. We need to lay the foundations, right? Can't build a house unless the foundations are strong. Don't you think? Yes. Let's build the house of endocrinology. So we should begin by just outlining that

Well, what needs to happen? And so we're in the context of exercise. Yeah. What needs to happen in the body during exercise homeostatically? What kind of things is the body trying to regulate? Well, great question.

Exercise causes numerous homeostatic challenges. It tries to push a whole bunch of things out of whack. Blood pressure, body temperature, blood glucose, just to name a couple. Blood volume. All those things need to be maintained and it's not easy. So the hormones need to jump in and say, hey, don't worry, fam, I got this. And that's how they work. Well, it's not how they work, but it's what they do. So to understand the hormones...

First thing that I get asked a lot from my students is, listen, Dr. Mike, you idiot. I need to... I don't know why they say that last part. But anyway...

I know that we've got two communication networks of the body. We've got the nervous system, which uses neurons. It senses what's happening in the external. It's like phone calls. Yep. It senses what's happening in the internal external environment, detects the change and elicits a response. But we've also got the endocrine system that can do the same, detects what's happening in the environment and elicit a response. How the hell are these two systems different? And do you know what I say to them?

Go read a book. Okay, go ask Dr. Matt. So Matt, what, in what way are they different? Yeah, to make a very simple analogy, I think... Which are the only ones you can make. That's right. The nervous system is like a phone call, very direct, quick, fast.

to one area, one person. Yeah. Right? Whereas hormones are like your flying airplane you throw out the back of the airplane, a whole lot of pamphlets. That's going to scatter everywhere. Yeah. A lot of people will get the message, take a long time for it to finally settle down and get it. But it goes everywhere. It goes everywhere. Yeah. I like that. There's still a communication method, but one's faster and direct, one's slower, more diffuse. Perfect. Yeah.

direct, faster, shorter acting, right? That's another point. But also the chemicals that they release are called neurotransmitters. And then the endocrine system, diffuse, slower, longer acting, and the chemicals that they release are called hormones. So we're dumping now these hormones into the bloodstream. So my next question is,

How do we classify these hormones? Yeah, so the classification is based on what the hormones made out of. Mostly. I'm sure the study of hormones and how they work is termed endocrinology. And you can't pronounce it, let alone do it. I would say that most hormones would be classified on their chemical structure. But there's probably other ways to do it. But that would be the main one. So what are they?

Well, some are made out of proteins. So we call that protein-based hormones. Yeah, makes sense. Some are small proteins, which are peptide. Yeah.

Have you got an example of that one? Insulin maybe? Well, the difference between... Firstly, what makes something a peptide versus a protein is the number of amino acids. So if it's less than 100 amino acids, it's a peptide. More than 100, it's a protein. But like you said, yeah, you could say insulin. Generally, the peptide and protein hormones are in a single category. Okay. So you can say the peptide slash protein hormones. So there's that. What's another category? Then...

Single amino acids. Yep. Or at least amino acid derived from one amino acid, Matt. What is that one amino acid? Tyrosine. Beautiful. Okay. So you've got that one. And then you can go to the ones that are made out of cholesterol or steroids. So steroid-based. Yeah. So we've got amino acid derived, i.e. tyrosine-based.

Protein slash peptide-based and steroid-based. Okay, beautiful. Now, just quickly, just so people understand, the most abundant are the protein peptide-based. They're the most abundant. If you want to know where these hormones categories are predominantly located, you can say, okay, amino acid-derived, tyrosine, these are...

produced in the adrenal medulla. So these are adrenaline, right? Predominantly. But thyroid hormone as well are tyrosine-based. The peptides and proteins, basically all the pituitary gland hormones, both anterior and posterior, they're protein-slash-peptide-based, but also the pancreas. So insulin and glucagon, protein-slash-peptide-based. The steroids, they're based or they're produced from the adrenal cortex, not the medulla, but the cortex, right?

So this includes aldosterone, cortisol and the androgens, but also the gonads. So this is going to include estrogen, progesterone and testosterone. And maybe the skin if you include vitamin D.

Yeah. Yeah. Well, yeah, you could. I think that's now... Is that a hormone or a vitamin? I think it's more of a hormone now. Okay. So let's have a think about if I said to you, Matt, all right, you know, I've just given you an example, right? That the pancreas has protein slash peptide hormones, but I want to stimulate the pancreas to release. No, actually, I'm going to annoy you and interject, and then I'm going to get threatening emails for doing so. Yes, what would you like?

The first thing I'm going to say here, again, your students are going to go, all right, so Mike, you just told me at the category, who cares? Why do I need to know this? Why do we have to classify hormones based on their chemical structure? Who cares? And again, why are your students so – We can get to that now. And my students are actually very kind to me, Matthew, just so you know. Okay.

Why? Great question. Let's talk about it. The protein slash peptide slash amino acid based hormones, because they are all ultimately amino acid based and amino acids have a charge associated with them, predominantly a negative charge. We know that when they're dumped into the bloodstream, which is mostly water, which also has its amphipathic, so it has both a positive and negative charge.

that it mixes with the water beautifully. So amino acids, proteins, peptides, they freely move through the water. Soluble. Soluble, no problem. But when they get to their target tissue, because they're charged and we know that- And they're large as well, large and charged. Large and charged, baby. They can't get into the membrane. The fatty acid membrane, that's right. So they need receptors on the surface and when they bind to those receptors, they trigger intracellular-

called secondary messengers and that's a whole complex... There's a range of secondary messengers. G-proteins, tyrosine kinases, things like that. C-A-M-P, all this. Yep. There's a whole range, too complex to talk about but effectively...

triggering them results in the cell itself doing something. Yeah. Right. Having its effect. All right. Also just iron channels as well. They can just open doors. Yeah. So the water soluble hormones must function through a surface receptor. Then you've got the steroid hormones because they're fat based.

Cholesterol-based. They can't move freely in the bloodstream because we know that fats and waters don't mix, so they need to bind to a carrier such as albumin, right? So usually a protein. Yeah, produced by the liver. That's an important aside. I know we're talking about exercise physiology, but if most of the carrier proteins are produced by the liver and the liver is dysfunctional and can't produce the carrier proteins, that affects the hormone, the free hormone balance of the cholesterol-based hormones within the bloodstream. And that's important because that changes their effect. Yeah.

So it carries steroids to the target tissue but then must release them and then they can move freely through the fatty membrane and they have their effects on intracellular or cytoplasmic receptors which then transport it to the DNA and allows for it to have its effect on more receptors on the DNA changing transcription and translation. So going back to just a second, you spoke about the transport effect of hormones. Yeah.

Let's stick in the space of exercise. How may exercise influence hormone levels? Well, outside of stimulating them or inhibiting them in response to various stimuli, it's

you can actually change their concentration by changing the blood volume. So we know you exercise, you sweat, you remove fluid from the body, your blood volume changes, diminishes, but that means the things that are in your blood, their concentration goes up. So they don't go out with the sweat? No, the hormones won't be... Too big. Yeah, that's right. So you can increase your concentration of hormones in your bloodstream by

by reducing your blood volume during exercise, which can theoretically increase their effects. So there's no point in me anymore drinking your sweat if I wanted to get access to... Firstly, that makes me sick. Secondly, when have you been doing that? Is that why you always ask, oh, are you finished with that T-shirt that you were wearing doing burpees? And then it comes back and it's all round out into a glup, a glup, a cup, this glass of this...

very thick looking horrible water like fluid and you scull that right down. Gross. You're disgusting. So let's... What else though? What do you mean? Just to test your... What other exercise effects? So we've got obviously... So what determines the hormone in the blood? We've obviously got how much is secreted.

Now let's just assume exercise doesn't have a huge role there. Okay. Okay. Besides just needing the stimulation for the exercise. But in terms of unlike what you said with the plasma volume, which is more profound to likely to occur in exercise, what else could happen to change the concentration of a hormone in the blood? Well, just as a drug would be impacted by its metabolic activity,

and its clearances. So how the hormone is metabolized and how it's gotten rid of will determine its concentration and its potency in the blood, right? And exercise affects that? Yeah, because the two organs that do that would be the liver and the kidneys. And as we know, with exercise, we usually shunt blood away from those regions. So they aren't necessarily metabolizing and excreting the hormones as quickly as they normally would. So that would also impact...

the concentration of some hormones while we exercise. Cool. Okay. Good to know. How do we stimulate these hormones to be released? So it goes to your question now. Yeah. So I'll just reiterate the question I had before. I'm so sorry for talking while you were interrupting. Um,

We have the pancreas and I said earlier, it was a long time ago now, but I said that the pancreas produces peptide slash protein-based hormones. How do we trigger the pancreas to release those hormones? Now there's three main types of stimuli to release hormones from glands, cells, tissues or glands, right? Because that's the... We didn't even define endocrine. We said that what they did... Okay, endocrine... Endo means cell crying. Self crying. Cell, cell crying. Cell crying, right.

They're not crying tears. They're crying tears of hormones. Okay. From a gland, so a cluster of cells into a blood vessel.

Yeah, that's pretty much it. Cells, tissues or glands that release hormones slash chemicals into bloodstream. All right, what stimulates them? So the three main stimuli, you've got a neural stimuli. So you can have the nervous system stimulating it to be released. You can have a hormonal stimulus where a hormone actually stimulates the gland to release. And you can have a humoral stimulus in which you can have a nutrient, for example, like glucose, stimulating it to be released. So these are the three stimuli. So do that for insulin then, go for it.

Oh, well, yeah. So you can have the sympathetic nervous system innervating the pancreas and it stimulates it to inhibit, for example, insulin to be released or stimulate glucagon to be released. The neighbor. Yeah. So you can have a hormonal response. So you can have... So what would... Sorry, from a nervous stimulation point of view, what would actually release insulin?

From the nervous system? Yeah, yeah. Well, the nervous system innervating it releases noradrenaline. But in terms of is there a nervous response that would actually tell the beta cells to release noradrenaline?

Insulin. And I'll answer that and say, yes, it's the parasympathetic nervous system. Beautiful. Thank you very much. The hormonal is the hormone. So you can have hormones released from other parts of the body like the digestive tract that can stimulate the pancreas to release insulin, for example, after feeding. That's actually the most profound means of insulin secretion. They're called incretins, which we spoke about a few podcasts ago.

different series, not the exercise one, but basically when you eat food, most people would think when you eat food, particularly with a lot of glucose or carbohydrates in it,

The actual blood sugar levels is the biggest stimuli for insulin release. But it's actually the incretins, which are the paracrine hormones from your gut that go to the pancreas and one being the glucagon-like peptide, which is where the Zempic medication works. That actually is quite a large hormone.

cause of insulin release yeah so that's another hormone so that's yep hormonal stimuli and generally speaking when you have a look at hormones that are released that then go to another gland to trigger the release of another set of hormones they tend to have the suffix tropin on their end okay so just so you know that and then the last one is the humoral release so this is nutrients within the bloodstream uh this can be you know

vitamins, minerals. They can also be actual nutrients like glucose, for example. And in this instance, again, with the pancreas, glucose can tell insulin to be released. Okay, so let's now... Have we done enough of a background for the endocrine system? I think we have. Let's jump into the hormonal control of insulin.

Utilizing substrates. Okay. Fuels for exercise, during exercise. So first thing that we need to keep in mind is this. We said it in the last episode, we'll say it again, is that during high-intensity exercise, which by definition can't go for very long. So it's high-intensity, short duration. What would that be in VO2? This is going to be above 70%-ish VO2. Okay. Right? Right.

So very heavy to severe. Yeah, close to 100% that your body is going to be preferencing carbohydrate oxidation. So using carbs for energy, right?

When you do low intensity for a long duration, so sub 50% VO2 max, your body will be shifting to fat utilization or fat oxidation for energy. So keep that in mind because we will sort of explain the reason why that's the case in a sec and it makes total sense if we explain it well enough.

So there's a couple of things that we need to understand. And the first thing is that the way that the hormones work in this instance to determine are we using carbohydrates or fatty acids have to do with these three things, right? One, it wants to tell the muscle to use its own glycogen sources preferentially. Secondly, it needs to maintain blood glucose levels predominantly by mobilizing glucose from the liver.

Right. For the muscle or just for the whole body? Again, it just wants to maintain blood glucose levels broadly by mobilizing glucose from the liver. And it can do that by telling the liver to break down its glycogen that it has stored or by making new glucose through gluconeogenesis. And then the third thing is by mobilizing free fatty acids from adipose tissue into the bloodstream. So these are the three major things. Tell the muscle to preferentially use its own glycogen.

Free the free fatty acids from the adipose tissue so that the muscle can also use that as well preferentially or to spare the glucose from the bloodstream and also to maintain the blood glucose levels via the liver by telling the liver to break down glycogen to glucose but also telling the liver to make new glucose through gluconeogenesis. And this is how the hormones work by basically doing all three of these things during exercise.

Let's first start with telling the muscle itself to use its own glycogen. The predominant hormone in this instance is what? Well, if it's a hormone, I said hormone. The predominant hormone in this instance is what? Oh, you want a one-word answer? I want a one-word answer. Adrenaline. Okay. Why?

What's going on? Well, if it's an extreme bout of exercise, you're in a high stress situation. Beautiful. And so your body is responding to this high stress, which is a fight and flight response. Absolutely. Which is a combination of the neurotransmitter fight and flight, which is more noradrenaline, and the fight and flight response coming from your adrenal gland, which is more adrenaline.

Yeah, exactly right. So you possibly could say that the big difference between adrenaline and noradrenaline in this regard is noradrenaline's playing more of a role around the sympathetic nervous system. So trying to maintain your background systems to be working like

like your cardiovascular system, your respiratory system. Yes. So telling the heart to increase its rate of contraction, force of contraction, telling the airways to relax and dilate, telling the blood vessels at the muscle to dilate and relax, telling other blood vessels to constrict, to shunt the blood to the muscle. So yep, that's true. And then adrenaline is probably playing a more profound role in regulating the blood sugar for this particular stressful event. Love that. I think that's, I think that's really, really a nice way of putting it. So yeah,

So what adrenaline predominantly does in the latter, so what we're focusing here is the nutrient or the fuel utilization, right? So we're not talking about those other things like increased heart rate because we're going to go through organ systems of exercise physiology in future episodes. So here's just talking about mobilizing the substrates.

So the latter thing that you spoke about. So what adrenaline does in the bloodstream is it's a potent stimulator of glycogenolysis, right? So taking glycogen, stored glucose, breaking it down to free glucose. So there's been heaps of studies that have shown that as your exercise intensity goes up,

your glycogenolysis goes up. That makes sense. Freeing glucose to be used for that. And we said high intensity means more glucose utilization, right? But we also have evidence that shows that as the intensity goes up, our adrenaline also goes up, which means that you could go, well, if they all go up together... Cause effect. Cause effect that the adrenaline stimulates glycogenolysis. And that's true. We definitively know that that's the case. However...

What if I gave you a drug that blocked your adrenaline? What would you expect to happen? Well, it then should stop. Yeah. What would stop? The glycogen breakdown. But then we'd have no glucose. Technically. Technically. Do you think that the body would allow this to happen, Matt? Well, you wouldn't think so. No. You wouldn't think so. And just to underscore that, if you were to do 100% VO2 max,

I know you wouldn't be able to sustain it for very long, but if you were to do it for like five minutes, you would almost use most of your glycogen stores. Yeah. And that, like you said, nicely. Within the muscle. Within the muscle. That correlates very tightly. So if you were to graph that, you would actually see, and the graph being the glycogen in the muscle versus time. Yeah.

based on intensity, you would see it would plummet straight down. Likewise, if you were to graph the intensity, the same thing, but then look at blood levels of epinephrine or adrenaline, it would be an inverse relationship. One would be spiking up, one would be spiking down. So like you said, you'd think, well, the two are...

have a tight, neat relationship. So therefore, that's the end of the story. Yes. But then obviously scientists don't like to just end it there. So they'll... Let's use a beta blocker. Let's use propranolol, which is a beta blocker. And then we... What does that mean to be a beta blocker? It blocks the receptors that...

adrenaline would bind to. Okay. In this case, the beta receptor being on the muscle that, so going back to what we spoke about a bit earlier with a hormone jumping, well, a hormone that can't get into the cell, it binds to the receptor on the outside of the cell. Yeah. Right.

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With 365 by Whole Foods Market and gelata and mole sauces. Shop Whole Foods Market in-store and online. What adrenaline would be doing is it would bind into a beta receptor on the cell and would activate a series of G-protein and a series of second messenger systems, which ultimately would turn on an enzyme that would start chopping up glycogen. Yes. So if you were to block that receptor...

So now adrenaline can't activate that process. You would think, well, the enzyme's not going to get turned on. No glycogen. But they found that regardless of before or after propranolol, you would still get the same degree of glycogen breakdown. So that tells me the body has some inbuilt redundancy. So it says, okay, not using adrenaline here to break down glycogen into glucose. Let's use something else. What is this something else?

Calcium. Calcium. Okay. Now, to me, that makes sense because one of the downstream effectors of adrenaline is releasing calcium.

And so my assumption would be that released calcium during muscle contraction. And did that happen? Absolutely. Remember your muscle has these big, the muscle has endoplasmic reticulum that are modified just to store calcium. Big swimming pools. What are they called? Psychoplasmic reticulums. Yeah. And so when muscle contraction occurs, we stimulate the psychoplasmic reticulum to release the calcium into the muscle tissue itself and

This needs to bind to certain things like Calmodulin, for example, to tell it to contract.

In skeletal muscle itself, you've got a whole range of different things that the calcium is the key to unlock tropomyosin and so forth. But effectively, the calcium does many more things in addition to just telling the muscle to contract. As we've seen here, it is the stimulus to tell glycogen to break down to glucose. So both adrenaline and calcium are potent stimulators for glycogenolysis. Yeah. And how do they...

Just out of interest, how do they test for that just to confirm that as a phenomenon? Well, I assume they would have to block the calcium. Well, that wasn't the answer I was looking for. Oh, okay. They did experiments where they just exercised one muscle. Right. Oh, I see what you mean. Okay. All right. So if, for example, we know that adrenaline –

stimulates glycogenolysis, but adrenaline is dumped into the whole bloodstream. So effectively, wherever I measure the adrenaline in your body, it should be the same levels, right? But if you jumped on a machine, let's just say leg extension to work your quadriceps. So only the quadriceps are contracting. On one leg. Yes, on one leg, making ATP and utilizing ATP.

You would assume that if the neurodrenaline is everywhere and it's a potent stimulator glycogenolysis, then every skeletal muscle would equivalently break down glycogenolysis. Yeah. So if I then did the biopsies in both legs, you would assume that it would be equal in terms of the amount of glycogen in my muscle. Yes. But that's not the case. That's not the case. They found that in the exercising muscle that the amount of glycogen was less.

Which tells us that it can't be solely adrenaline. So calcium is the case. Brilliant. So this is one of the ways that the muscle itself preferences glycogen

for energy to make glucose is by releasing the adrenaline through the sympathetic response, the stress of the exercise, which goes up with the intensity. And like I said, the more intense the exercise, the more we want to use glucose. That's great because the more intense the exercise, the greater the contraction, the greater the calcium, the greater the adrenaline. All the right things go up to tell us to say glucose, glucose, glucose from your own supply.

But as we know that it's not only just going to stick to the glucose within the skeletal muscle, right? We know that skeletal muscle can suck in glucose from the bloodstream and that the more that you do physical exercise, the more demand the skeletal muscle will have on sucking the glucose from the bloodstream. And we know that skeletal muscle, you know, will increase 10 to 20 fold its blood flow, its demand, everything, which means it could very quickly suck that glucose away. Right.

So, for example, during intense exercise, you can burn about one gram of carbohydrates per minute from the blood plasma. So you can use it super quickly. And how much does the, let's say, the liver have? About 80 grams. So you could technically get through it in 80 minutes. The blood plasma. Yeah. Yeah. If...

meaning that the liver is the primary way we replenish it, right? So as we're sucking away and burning that one gram per minute from high-intensity exercise from the blood plasma, the liver needs to break down its 80 grams of glycogen into glucose and dump it back into the bloodstream to maintain it.

If it can't maintain it, one, fast enough or at the end of the day, at the end of the whole exercise or during, you become hypoglycemic and the brain doesn't get its glucose and you collapse. You can't do anything, right? Your brain doesn't function. You don't function. So the point I'm trying to get across here is that the next thing we need to be able to do is maintain blood glucose levels even though the muscle is starting to suck away some of that glucose, right? Now, how do we do it? We do it by...

Like I said before, triggering the liver to undergo glycogenolysis, triggering the liver to undergo gluconeogenesis. And what's that mean again? Taking non-carbohydrate based sources like lactate, free fatty acids and glycerol and amino acids to make glucose.

We can mobilize free fatty acids from adipose tissue and dump it into the bloodstream. You might think, but that doesn't increase blood plasma. But what it does is now you've got an alternate fuel source in the bloodstream that the muscle can pull upon and other tissues actually to utilize as energy and spare the glucose in the bloodstream. And then finally, the hormones that get released naturally

which we're going to talk about, in addition to doing all those things I just said, they can block the entry of glucose into cells and tell them, hey, use fat as your primary fuel source. Instead of glucose. Glucose is brain. That's right. You guys use fat. Exactly right. Now, a lot of the time, like I said, you can't maintain high-intensity exercise for a long period of time. The amount of high-intensity exercise that you can maintain is pretty much –

solely going to be the energy is solely going to be provided by the glycogen within the skeletal muscle give or take it obviously utilizing other sources from the bloodstream and so forth but predominantly that's it just to underscore that

Like I said a bit earlier, if you were to do that VO2 max of 100%, you'd get through your glycogen within five minutes or 10 minutes. But if you were doing a VO2 max... Glycogen from the muscle you're saying? Yes. Okay, yeah. But if you're going to do VO2 of 30%,

you'd only gone through, after two hours of exercise, you've only gone through 20% of your glycogen. Yeah, and a big reason is because of the reduction in epinephrine because you don't have such a big epinephrine, sorry, adrenaline spike, right? Yeah.

Same with the calcium. And in addition, you're not utilizing the fast twitch fibers, which predominantly want to use glucose. You're using the slow twitch fibers that want to utilize free fatty acids predominantly. So in order to do all those things, maintain the plasma glucose by all those things I said, glycogenolysis, gluconeogenesis, mobilizing free fatty acids and blocking the entry of glucose into cells, we need hormones.

And you can break those hormones up according to how fast and slow that they perform. So you've got the permissive, the slow-acting hormones, those that allow for you to increase blood glucose levels, right? They're slow-acting. They're bubbling away in the background, allowing for all this to happen during exercise. So these hormones are thyroid hormone, cortisol, and growth hormone, right? So...

thyroid hormone released by the thyroid t3 t4 yep so there's two thyroid hormones but most of it's turned to t3 at the tissue that's the functional one yep what does thyroid hormone do what does t3 do simply put it just regulates your metabolic rate so how fast your cells are burning through or producing atp burning through those systems we spoke about last week

So that's primarily what it's there for. But it can also preference certain fuel sources. That's right. So it's good for mobilizing fat. Yeah. And it also is important for making the adrenaline system more... Potent. Potent or more sensitive. Yeah. So it changes the amount of...

of receptors for adrenaline. So it doesn't change the objective amount of adrenaline in the body, it changes the receptors. Yeah, and that's important to state here. We didn't mention it earlier, but when we spoke about the receptors on the outside of the cell, they're not static. They're always changing. So it's a dynamic system. So...

If the cell is overstimulated by a hormone or a drug, it will downregulate it. It will kind of go, this is way too much. This is too much stimulus. I'm going to stop making receptors. So the quantity of the receptors on the outside of the cell membrane starts to drop away and the same goes in the opposite direction. If it feels like it's not stimulated enough, it might upregulate and produce more of them. So in this case, T3 upregulates T3

more adrenaline-like receptors, adrenal receptors, and make the affinity for the hormone on the receptor more pronounced. So that means it can help the glycogen utilization within the muscle? Yes.

but also mobilizes free fatty acids. Yeah, and you can see this in situations where there's too much thyroid hormone. So this would be hyperthyroidism. Yep. You would see a profound sympathetic-like response. Yeah. So they're fast heart rate, fast breathing. They lose a lot of weight. They're highly agitated. Sounds like you're describing me, Matthew. And they can't sleep. Okay. Well, you've ticked all the boxes for me. So that's underscores...

In an exaggerated example of what the thyroid hormones do. Yep.

The next is cortisol. So cortisol, we term the stress hormone, which, you know, it does increase during times of fight or flight. Definitely, yes. But this makes sense because we are talking about adrenaline today, right? And its role during exercise, which is a fight or flight response, right? I mean, exercise is a stressor. So, of course, cortisol goes up when you undertake exercise. Right.

And its job is- What's its name? What's its name? Other name for it. Glucocorticoid. So there you go. So, well, explain that. You can't just say, there you go. Explain. What does- Glucose. So it's a hormone that plays an extremely important role for ensuring glucose is in your blood. Yeah, true. And the cortico part means it comes from the

the cortex of your adrenal gland. Perfect. Yeah. Okay. So the oid part means it's a steroid. Steroid. So oid. Oid. Oid. Yeah. Glucocorticoid. So it's,

Plays with glucose, comes from the cortex of the adrenal gland and it's a steroid. All that makes sense. What does it do? Mobilizes free fatty acids. So it tells the fats from the adipose tissue to dump free fatty acids into the bloodstream, preferencing fats as an energy source for the body as opposed to glucose, so sparing the glucose. It also does the same or similar with proteins, tells the proteins to break down to amino acids,

but they can go to the liver to use for gluconeogenesis to make more glucose. It also decreases glucose utilization by cells, maintaining blood glucose levels. So...

So predominantly it's going to be – this is an interesting point, right? Because if you say, wait a minute, isn't the whole reason here to make sure there's enough glucose for the cells to use but it's telling the cells to use less? It's telling the cells to preference fatty acids. That's one thing. To maintain so that the brain – it's not telling the brain to not use glucose, just so you know, right? The brain is always going to use it because the brain takes glucose in. It likes it.

through a concentration gradient. So when the brain is deficient in glucose and the bloodstream is higher in glucose, glucose just falls into the brain effectively, right? So a lot of this is to make sure that the brain maintains its glucose levels. Otherwise, nothing works. So that's cortisol. Then the last one is growth hormone. So growth hormone, what does that generally do? Firstly, where's the growth hormone produced?

Anterior pituitary gland. Yep, beautiful. And I think most of its profound effect is its effect on the liver to produce another, would you say another hormone? Yeah. Insulin growth factor. Yep. That can also tell the skeletal muscle to produce it.

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included with your Prime membership. To start listening, download the Amazon Music app for free or go to amazon.com slash adfreepodcasts. That's amazon.com slash adfreepodcasts to catch up on the latest episodes without the ads. Okay. Yeah, directly, yeah. IGF-1. So it has an effect on... Protein synthesis. Yeah, yeah. So that as a hormone...

We know, again, in excess, we'll exaggerate growth depending on particularly bone and muscle, right? So growth hormone itself. Yeah. If it's before puberty, it would cause the person to get quite large in stature. Whereas if it's after puberty, it would just cause certain body parts to kind of grow in size.

And that's because the bone plates have closed over. So, yeah. Okay. So what the growth hormone does is it tends to decrease glucose uptake by the tissue. So it's very similar to cortisol in this sense. Probably just less protein breakdown, I guess you'd say, right? Yeah, that would – yes, agreed. Okay.

So decreased glucose uptake by the tissue, increased free fatty acid mobilization and increases gluconeogenesis. So thyroid, cortisol and growth hormone, these permissive slow acting hormones that get released during exercise, they're there to maintain blood glucose levels, one, so that if the muscle needs its

It's there but predominantly so that the blood glucose levels are at a good level for the brain to be able to utilize it for energy, okay? But now we've got the fast-acting hormones. These are the ones that very quickly return our plasma glucose to normal, right? Because like I said, one gram per minute can be burnt away from the bloodstream if going unchecked. So predominantly this is adrenaline and noradrenaline, right?

So we've already spoken about what they do in the skeletal muscle, helping break the glycogen down into glucose for the muscle specifically, but it also has systemic effects outside of the muscle itself. So it can mobilize glucose from the liver into the bloodstream, mobilize free fatty acids from adipose tissue into the bloodstream, and again, decrease glucose uptake from the tissues as well. So I think that's important.

Yeah, and depending on which receptors we're talking about here, because the adrenal... These are adrenal receptors, right? And they have different effects in different body regions. So we have the alphas and the betas. And so some would act...

solely on fat tissue. Some will act on the pancreas and that will play around and glucagon. So that would determine if insulin is being inhibited and glucagon has been released. And then we have certain systems where the cardiovascular system or the respiratory system is being more

I guess you'd say. Yep, exactly. So also the adrenaline we said earlier, you know, it goes up with the intensity of the exercise, but during prolonged or endurance training, adrenaline rapidly decreases, right? Which then means that, well, there's going to be less glucose mobilization into the bloodstream. Uh, and there's going to be a more preponderance for the tissue to use fats, the muscle tissue to use fats, right? So, uh,

Which makes total sense because then we're shifting from using glucose to free fatty acids. So do you think that makes sense from an athlete standpoint? So if we, as we spoke about a bit earlier, if you are, we know that when we're exercising, particularly with a slightly higher intensity, we want to be using glycogen in our muscle. Yeah. And we know that, not the full story that adrenaline plays a role, but it's half of the story. But you would assume by...

Increasing the amount of adrenaline, you'll be producing more breakdown of glycogen. Yep. But as an athlete, you probably don't want spiking to happen, right? You want to probably have the adrenal or the adrenal system, adrenaline system, what would you call it? Adrenergic. That system to be a bit more controlled so you're not having like big fluctuations. Yeah.

So you're ideally, particularly if it's an exercise that you're wanting to increase the duration for, you're really wanting to ensure that the muscle is using those long energy sources, right? Like the fats. Yeah. The way I see it is that, you know, if you're an athlete, if you're doing a high intensity exercise, you need glucose. So insulin goes, sorry. So adrenaline goes through the roof. Yeah.

with the intensity, mobilizing the glucose from the glycogen in the muscle to be used for the energy. But what it doesn't want to do is tell the muscle to suck all the glucose from the bloodstream, right?

So when adrenaline does get released into the systemic circulation, right, not just the muscle itself, but it goes, look, let's maintain our blood glucose levels by telling the liver to increase more glucose, but let's also release free fatty acids into the bloodstream so that if the muscle does try and take out glucose, which it will, we've got the glucose there because we're telling other tissues to use free fatty acids, but there's also free fatty acids there for the muscle tissue to utilize. Right.

But as the intensity drops down and you start to do more endurance exercise, you don't want to – because you're changing the fiber types that you're using from the glycolytic to the slower twitch fibers, the adrenaline goes down with it. So then the glycogen is spared within the muscle tissue itself. For the intense bursts. It's spared so that it can be used for the intense bursts, yeah. But for the endurance, it's spared.

so that it can utilize free fatty acids as a fuel source. And that's what you're saying in terms of training. If you do endurance training, you actually become more efficient with your adrenal system.

Exactly right. Yeah, exactly right. Now, the last two hormones we need to talk about are the counter-regulatory hormones, which we call insulin and glucagon. These hormones we already know about because they are important. They're released during fed and fasting states. After a meal, blood glucose levels go up, triggers insulin to be released from the pancreas and

And insulin's job predominantly is to tell the cells to suck up, so increase their uptake of not only glucose but amino acids and fatty acids and increase the storage of glucose, amino acids and fatty acids. Therefore, insulin's job is to reduce blood plasma levels of those substrates, right?

glucagon does the opposite. It's the flip side. So when you're in a fasting state and your blood glucose levels drop, glucagon is released again from the pancreas, increases the hydrolysis of glycogen into glucose, increases free fatty acids and proteins to be broken down to amino acids, and also increases gluconeogenesis. It's actually a potent regulator. One of the strongest regulators of gluconeogenesis is glucagon when it's high. Glucogon.

Insulin inhibits gluconeogenesis. So the ratio here is very important. You need to have low insulin and high glucagon for glucagon actions to be predominant and vice versa, low glucagon and high insulin for the insulin factors because they very strongly negatively regulate each other. So if insulin is high and glucagon is high, you're going to have –

Weird effects. Exactly right. Which can happen in diabetes, right? Correct. So glucagon's job is to increase blood plasma levels of the substrates. And so you can – it makes sense that what you'd probably want to do during exercise is – now, okay, let me ask you, right? I've said insulin tells the tissues to suck up glucose amino acids and fatty acids and promotes their storage. Right.

During exercise, the demand that the muscle has for blood and nutrients goes up 10 to 20 fold. And I just said insulin tells tissues to suck these things up. So wouldn't you think that with increased exercise intensity that you'd want insulin to go up because it increases cells sucking the nutrients up? Yeah. Is that what happens? And on top of that also just the fact that the blood sugar is going up

then you would expect insulin to go up with it because that's just, like you said at the start, insulin release is dictated by substrates, like in this case glucose. So you'd think while you're exercising and you're releasing all this glucose from the liver...

your insulin should be excreted because of the blood sugar being not high, high after like after a meal, but high enough to warrant insulin release. So does insulin go up with exercise? No, it actually gets blunted. So both from the effect of...

So adrenaline, like we spoke about the different receptors, there are receptors on the pancreas. There's receptors for glucagon, which will tell that to release. But there's also receptors on the beta cells that would tell it to inhibit. Tell insulin to be inhibited. That's right. So insulin goes down, one, because the adrenaline that's released from the stress of the exercise inhibits it. But then the question is, so how does the –

What happens with the muscle? Does that mean the muscle doesn't get any of the glucose from the bloodstream? Yeah, so typically you would think that would be the case because where insulin normally has its effect is on two tissue types, fat tissue and muscle tissue. They're insulin dependent. That's right. And so you would think that with low levels of insulin that now muscle can't access its glucose. But in fact...

When the muscle is exercising, it's getting greater blood flow, getting greater glucose transport to it.

the sensitivity of the insulin receptor increases during the exercise. So what insulin is there, it's responding better to. Even though insulin is low, it's more sensitive to it. That's right. And at the same time, within the cell, it's producing more transporters independent of insulin. Normally, it needs insulin to transport those receptors up to or the carriers up to the membrane of the muscle cell. But now without insulin,

insulin does it on its own. So let me just clarify. We said earlier that during exercise, particularly high intensity exercise, we want the muscle to use its own glycogen preferentially over the blood glucose. But here we're saying that the muscle tissue will take the glucose. And that's true. We didn't say that the muscle doesn't. We just said that the body wants it to preference its own glycogen. And so what

What the drop in insulin does is it sort of allows for the blood glucose to remain higher, so help maintain blood glucose levels while the muscle tissue tries to suck that glucose in. It will suck that glucose in inevitably for all the reasons that you said. Increases its sensitivity to insulin. There's a concentration gradient that brings the glucose in. There's more glucose transporters. There's an increased blood flow to the muscle tissues, all those things. So don't get us wrong.

The body will try and tell the muscle tissue during intense exercise to preference its own glycogen, but it will also pull upon the blood sugar as well. But the body is trying to maintain the blood sugar levels at the same time by telling the liver to...

Break down glycogen into glucose and put it in the bloodstream. Tell the liver to undergo gluconeogenesis and telling free fatty acids to be mobilized from the adipose into the bloodstream so other tissues have alternative energy sources as well.

But also it just is hoping that the muscle is staying within a intensity level that it's just preferentially using fatty acids, not glucose. Yeah. Yeah. Well, that's exactly right. That's exactly right. All right. Matt, I think we've covered a lot in this particular episode.

The future episodes, which we're going to do on exercise physiology, we're going to start going through some more specifics in regards to organ systems. So we're going to be looking at different organ systems and how they respond during exercise. It's going to be great.

It's going to be very enjoyable and I hope you're enjoying it. If you do like it, please contact us, let us know, send us an email, admin at drmattdrmike.com.au or you can follow us on social media at Dr. Mike Todorovic on all those social media platforms.

please go to our YouTube channel and like and subscribe. Give us a five-star review on the podcast. Let us know if you are liking this series. We will be doing more Q&As soon, so please send us questions via the email and we will try and answer them. And apart from that, thank you for listening. Thanks, Matty. See you, mate.

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