Carbohydrate Metabolism During Exercise


Learn how muscle uses glycogen, how it takes up glucose from the blood stream, how it is broken down through glycolysis to pyruvate, burned in the Krebs Cycle or converted to lactate.


Exercise Physiology | Muscle Contraction | Muscle Fibers | Muscle Adaptations | Exercise Fuels | CHO Metabolism | Fat Metabolism | Oxygen Uptake | Cardiovascular Exercise | Respiratory Responses | VO2 Max | Temperature Regulation | Heat | Fluid Balance | Fatigue | Sprinting | Endurance | Genes | Practical Case Example


CHO Metabolism During Exercise 


Learn about carbohydrate metabolism during exercise. The lecture begins with an exploration into the process by which glycogen and glucose from both within the muscle and bloodstream, how glycogen and glucose are broken down through glycolysis to pyruvate, how pyruvate is then oxidized in the Krebs Cycle or converted to lactate. Learn how muscle glycogen is used during exercise based on exercise training intensity. The lecture will cover glucose uptake, regulation, output, oxidization, and lactate metabolism.

The next topic is carbohydrate metabolism during exercise, largely more prolonged submaximal exercise and we are going to focus on how the muscle uses muscle glycogen and how it takes up and uses glucose from the bloodstream. If you recall from this overview of energy metabolism in skeletal muscle, we are going to focus on glycogen and glucose from both within the muscle and outside, how it’s broken down through glycolysis to pyruvate, and that pyruvate is then oxidized in the Krebs Cycle or converted to lactate.


Sections 

  1. Muscle Glycogen Use During Exercise
  2. Regulation of Muscle Glycogenolysis During Exercise
  3. Training & Muscle Glycogen Use During Exercise
  4. Glucose Uptake During Exercise
  5. Glucose Uptake During Exercise – Sites of Regulation
  6. Regulation of Muscle Glucose Uptake During Exercise
  7. Contraction Signaling to Glucose Transport During Exercise
  8. Training and Glucose Uptake and Oxidation
  9. Liver Glucose Output During Exercise
  10. Regulation of Liver Glucose Output During Exercise
  11. Training and Liver Glucose Output During Exercise
  12. Regulation of Carbohydrate Oxidation – PDH
  13. Lactate Metabolism During Exercise
  14. Regulation of Lactate Metabolism During Exercise
  15. Training and Lactate Metabolism During Exercise

Muscle Glycogen Use During Exercise 


If we look at how muscle glycogen is utilized during exercise. The major determinants of the right of glycogen use are exercise intensity and exercise duration. You can see in this graph how with increasing exercise intensity there is an increase in the right of muscle glycogen breakdown. That overtime at a given exercise intensity, the rate of glycogen depletion decreases. As we’ll see in the lectures on fatigue, running out of glycogen during prolonged strenuous exercise is often associated with fatigue.

Regulation of Muscle Glycogenolysis During Exercise 


If we think about the factors that regulate glycogen breakdown during exercise, that might explain primarily the exercise intensity effects. We see that there is local control from factors that increase in the muscle notably calcium, which you recall from muscle contraction, increases in the muscle when the muscle contracts. Also the increase in inorganic phosphate that occurs when muscles breakdown ATP is another activator of the enzymes that breakdown glycogen during exercise. In terms of hormonal control of muscle glycogen breakdown, a major regulator is an increase in circulating adrenaline. As the exercise intensity increases and those plasma adrenaline levels increase, it binds to receptors on the muscle and through a series of steps activates glycogen breakdown in muscle. The higher the exercise intensity, the higher the adrenaline, the greater the muscle glycogen breakdown. We also know that the availability of glycogen in the muscle increases its own breakdown. So, if there are increased stores of glycogen, you tend to break them down at a higher rate.

There’s been some discussion and debate as to whether increasing the availability of glucose in the bloodstream has any influence of glycogen breakdown during exercise. To date, most of the studies would suggest that it has a fairly modest effect. In contrast, if fatty acid levels are increased in the bloodstream, that has been shown to slow the rate of muscle glycogen breakdown. And there have been some interests in nutritional strategies that serve to increase fatty acid availability with a view to change the rate of glycogen breakdown. Finally, an increase in muscle temperature that you see when you exercise in the heat is associated with a greater rate of glycogen breakdown. So, when athletics exercise in a hot environment, they often rely more heavily on their muscle glycogen stores. That has implications for the nutritional strategies that they need to adapt to those circumstances.

Training & Muscle Glycogen Use During Exercise 


Another important factor, which influences glycogen breakdown during exercise is training status. An important adaptation to training is an increase in the mitochondrial oxidative capacity of the muscle that’s associated with lower utilization of glycogen. You can see that both the aerobic and the so-called anaerobic utilization of glycogen is reduced after exercise training. This is a major adaptation, which is thought to contribute to the increased fatigue resistance that you see in well-trained subjects during prolonged strenuous exercise.

Glucose Uptake During Exercise 


If we turn our attention to glucose from the bloodstream, as a source of energy for contracting the muscle, we see again that both exercise intensity and duration impact on the rate of glucose uptake. You can see in this graph, the glucose uptake into contracting leg muscles at three exercise intensities. So, like this, an increased intensity, an increase in glucose uptake, and you also see that at any given exercise intensity, a progressive increase in glucose uptake. If the exercise extends for several hours, then over time, what one sees is a slow reduction in glucose uptake as the blood glucose levels decline. This is one of the reasons why ingesting carbohydrate-containing drinks is often used as a strategy by endurance athletes to maintain blood glucose levels and to maintain glucose uptake during prolonged exercise.

Glucose Uptake During Exercise – Sites of Regulation


In terms of the regulation of glucose uptake into muscle, we need to remember that this process occurs by facilitated diffusion and what that means is that we need a gradient for glucose to move from outside the muscle to inside the muscle. We need a special transport carrier molecule to help get glucose across the membrane. There are three main sites of regulation for muscle glucose uptake: the supply of glucose, the transport of glucose across, the plasma membrane by a protein that we know as GLUT4, and the intracellular metabolism of glucose, during exercise with a large increase in muscle blood flow we see increase glucose delivery to the muscle. There’s activation of the glucose transport process, and I’ll talk about that in a moment. During exercise the increase in metabolism through those glycolytic and oxidative pathways that we’ve spoken about means that glucose is rapidly metabolized and maintains the gradient for glucose to move into the muscle. In the post-exercise period, a very important process is the recovery of muscle glycogen. The re-synthesis of glycogen is the major metabolic fate of glucose that is taken up in the recovery period. Ingesting carbohydrates during recovery is an important way of maximizing the re-synthesis of glycogen during recovery.

Regulation of Muscle Glucose Uptake During Exercise 


If we look at the regulation of muscle glucose uptake during exercise, we see that those three processes that I’ve just mentioned are increased. There’s an increase in glucose delivery because of the increase in muscle blood flow. The GLUT4 transport protein, which normally resides inside the muscle cell moves quickly to the plasma membrane where it becomes a functioning glucose transporter. There’s been some debate as to whether the activity of this transport protein can be increased during exercise. At the moment, at least, there’s no evidence that that happens. Finally, as I said, if you increase the disposal of glucose through glycolytic oxidative pathways that will maintain the diffusion gradient into the contracting skeletal muscle. We know that the availability of other substrates will influence glucose uptake. If glycogen levels are high in the muscle we tend to see a lower glucose uptake. The availability of glucose in the bloodstream is very important because it sets the arterial glucose concentration for that diffusion gradient. So, if glucose levels are low during prolonged exercise, in the absence of glucose ingestion, you will tend to see a decrease in glucose uptake, and if you increase the blood glucose level by ingesting a carbohydrate drink and absorbing the glucose from the gut, you will see an increase in glucose uptake.

The effects of free fatty acids on glucose uptake are a little less clear compared with those on muscle glycogen. With some studies suggesting that increased fatty acid availability will slow glucose uptake, other studies have seen no effect. The important point to make in relation to glucose uptake during exercise is that it occurs independently of insulin. The processes that are involved in glucose uptake during muscle contractions are slightly different from those involved with insulin stimulation. And it’s for this reason that there’s a lot of interest in exercise as a way of improving glucose uptake in those diseases like diabetes where insulin doesn’t work as well. Another important consideration is that if you are Type I diabetic and you have to inject yourself with insulin. If that occurs in close proximity to exercise because the two stimuli are additive that can often increase the risk of premature hypoglycemia. That’s why exercising Type I diabetics often take candy with them to rapidly increase their blood glucose level if they feel that their blood glucose levels are going low or if they feel what’s called hypo. Finally, the adrenaline, circulating adrenaline, which increases with increasing exercise intensity, it’s well-described effects on muscle glycogen the effects on glucose uptake are less clear.

Contraction Signaling to Glucose Transport During Exercise 


Given that the translocation of GLUT4 from inside the muscle cell to the sarcolemma is very important in removing the plasma membrane as a barrier for glucose uptake. There’s been a lot of interest in the molecular regulation of this GLUT4 transport process. You can see in this slide a number of molecules and enzymes that have been implicated in this GLUT4 translocation process. Most attention has focused on two pretty fundamental changes in muscle. We spoke about those in the adaptations lecture, and that is the increase in calcium, and the change in energy status, which has an impact on a kinase, the ANP activated protein kinase. So again, local events in the muscle changes in calcium and changes in the energy levels within the muscle serve to stimulate GLUT4 translocation to facilitate glucose uptakes in the contracting muscle during exercise.

Training & Glucose Uptake & Oxidation 


Just as we saw with muscle glycogen neutralization after training, we also see a reduction in the reliance on glucose. This study was done using labeled isotopes of glucose, which enable you to measure glucose uptake and also the appearance of the carbon label in the expired breath, so you can measure oxidation. You can see that both glucose uptake and glucose oxidation, are reduced, after endurance training.

Liver Glucose Output During Exercise 


Now, it’s very important that the blood glucose concentration is maintained within a relatively normal range during exercise. This is the role of the liver during exercise. So just as you see an increase in muscle glucose uptake, there’s a parallel increase in liver glucose output. You can see here that the curves for liver glucose output are very similar to those with muscle glucose uptake. With an increase in exercise intensity and an increase in exercise, the duration will increase liver glucose output. You will note at the lower intensities here were the exercise duration is extended that eventually the liver is unable to maintain the same rate of glucose output and it starts to decline. In the absence of carbohydrate supplementation, it’s at this point if the muscles are continuing to take up glucose that the plasma glucose levels start to decline.

Regulation of Liver Glucose Output During Exercise 


In terms of the regulation of liver glucose output, it’s quite complex and there are redundant mechanisms. We see both feeds forward and feedback mechanisms. By feed-forward, we mean activation of the liver in parallel with the onset of exercise and it’s thought that various hormonal changes and perhaps even some of the sympathetic nerves may play a role. I’ll talk about that in a moment. There are changes in the pancreatic hormones during exercise, insulin levels tend to go down and glucagon levels tend to go up and restored these two signals playing the important role in allowing the liver to increase its glucose output during exercise. Circulating adrenaline can also act on the liver glycogen stores, which are then broken down to liberate glucose. The sympathetic nerves are thought to play a role although there have been some interesting experiments in patients who have had liver transplants and therefore the nerves to the liver have been cut. When they exercise, they’re still able to increase their liver glucose output. So, I think this demonstrates if you like the redundancy and usually when there are multiple mechanisms controlling a process, it means that that process is quite important. And we often see that in physiology with a number of regulatory control systems. Just like the muscle, if the liver glycogen store is increased. You tend to break down liver glycogen during exercise and have a higher liver glucose output. The primary feedback control of liver glucose output is the blood glucose concentration. So, if it increases, you tend to reduce the liver glucose output. One of the consequences of ingesting carbohydrate during prolong the exercise is that you actually blunt the liver glucose output because the glucose that’s being absorbed from the gut can compensate for any reduction in glucose output from the liver.

Training & Liver Glucose Output During Exercise 


There are two processes that the liver utilizes to produce glucose, it can break down glycogen and this is referred to as glycogenolysis or it can also take various metabolites produced during exercises such as lactate, glycerol and some amino acids, and convert it to glucose in a process known as gluconeogenesis. You can see in the left panel here, before training, the relative contribution of glycogenolysis and gluconeogenesis to the total liver glucose output. Furthermore, you’ll notice that after a period of training, just as we saw a reduction in muscle glucose uptake and oxidation, you can see a parallel reduction in liver glucose output. Interestingly that reduction occurs in both glycogenolysis and in gluconeogenesis.

Regulation of Carbohydrate Oxidation – PDH 


Glucose from the bloodstream and glucose units derived from muscle glycogen is broken down during a series of reactions that we know as glycolysis to produce pyruvate. This pyruvate has two main fates: it can either be converted to acetylcholine and enter the Krebs Cycle and be oxidized or it can be converted to lactate. In terms of the oxidation of pyruvate, the important enzyme, which regulates the oxidation of pyruvate and therefore the rate of carbohydrate oxidation is called pyruvate dehydrogenase. You can see in this slide that again, intensity and duration a major determinants of pyruvate dehydrogenase (PDH) activity. So, as you increase the exercise intensity, and you increase the rate of carbohydrate oxidation that’s associated with greater activation of this critical enzyme.

Lactate Metabolism During Exercise 


The other side of pyruvate is converted to lactate, and a curve that is quite well known is the increase in lactate with exercise of increasing intensity, and you can see in the left panel the exponential rise in lactate as you increase exercise intensity and this is related in part to the increased rate of glycogen breakdown. There’s been a lot of interest in what we term the lactate threshold or were you get this rather large increase in lactate. I’ll come back to that later in the course when we talk about limits to performance. But it is correlated with endurance performance and so there’s been a lot of interest certainly in the applied sports sciences about measuring the lactate response to exercise. You can see that when you exercise below the lactate threshold, there’s a relatively modest increase in blood lactate. Whereas when you exercise above the lactate threshold, you can see a steady rise in the blood lactate levels.

Regulation of Lactate Metabolism During Exercise 


In terms of the regulation of lactate metabolism during exercise, the production of lactate is really determined between the balance between the rate pyruvate production and the rate of oxidation. The levels of lactate that you see in the blood are in turn determined by how much lactate is being produced by the contracting muscle and how much is being removed from the circulation either by the liver in the process of gluconeogenesis or by the muscles because it’s known that contracting muscles can oxidize lactate. The muscle oxidative capacity will influence the ability of those muscles to utilize oxygen and the enzymes that convert pyruvate to lactate, and lactate back to pyruvate differ in their chemical activity. The composition of those enzymes will influence where the pyruvate converted to lactate or vice versa. The supply of oxygen to the contracting muscles is shown, being shown to influence the production of lactate. There’s been much about whether that’s a direct effect of hypoxia within the muscle. Or whether there are other changes accompanying low oxygen such as an increase in adrenaline, which will increase glycogen breakdown and lactate. As I said adrenaline will stimulate glycogen breakdown increase the rate of pyruvate production and therefore increase lactate production. And similarly, if you have high levels of muscle glycogen, because that results in greater muscle glycogen break down, you also see increases in lactate.

Training & Lactate Metabolism During Exercise 


Finally, one of the hallmark metabolic adaptations to endurance training is a reduction in lactate. You can see here, the muscle lactate levels before and after training with the characteristic reduction in muscle lactate after training. This is mirrored by changes in the blood lactate, which is also lower after training. The lactate threshold shifts to the right after training. As I said earlier, this is used in the applied sports sciences as a biomarker of training adaptations within the muscle. In recent years, there’s been a lot of interest in proteins, which transport lactate. The so-called monocarboxylate transporters or MCTs. An important isoform that increases after training is MCT1, and what this does is facilitate the uptake at lactate into muscle, and into the mitochondria, and facilitates the oxidation of lactate. Which is an important metabolic fate of the lactate that’s produced during exercise? So, you can say a number of factors influence carbohydrate metabolism during exercise. Primarily the intensity and the duration of exercise and training status have a major impact on glycogen, glucose and lactate metabolism.[6].


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    Carbohydrate Metabolism During Exercise was last modified: October 12th, 2019 by Derek Curtice