Hormonal regulation of metabolism during exercise

As noted earlier, carbohydrate and fat metabolism are responsible for maintaining muscle ATP levels during prolonged exercise. Various hormones work to ensure glucose and FFA availability for muscle energy metabolism. In the next two sections we examine how the metabolism of glucose and fat are affected by these hormones during exercise. Because carbohydrate is the primary fuel used during both  brief and prolonged exhaustive exercise, we first consider the hormones that regulate its availability.

Regulation of glucose metabolism during exercise

The heightened energy demands of exercise require that more glucose be made available to the muscles. Recall that glucose is stored in the body as glycogen, primarily in the muscles and the liver. Glucose must be freed from its storage form of glycogen, so glycogenolysis must increase. Glucose freed from the liver enters the blood to circulate throughout the body, allowing it access to active tissues. Plasma glucose concentration also can be increased through gluconeogenesis.

Regulation of plasma glucose concentration

Four hormones work to increase the amount of circulating plasma glucose:

• Glucagon
• Epinephrine
• Norepinephrine
• Cortisol

The plasma glucose concentration during exercise depends on a balance between glucose uptake by exercising muscles and its release by the liver. At rest, glucose release from the liver is facilitated by glucagon, which promotes both liver glycogen breakdown and glucose formation from amino acids. During exercise, glucagon secretion increases. Muscular activity also increases the rate of catecholamine release from the  adrenal medulla, and these hormones(epinephrine and norepinephrine) work with glucagons to further increase glycogenolysis. Cortisol concentrations also increase during exercise. Cortisol increases protein catabolism, freeing amino acids to be used within the liver for gluconeogenesis. Thus, all four of these hormones can increase plasma glucose by enhancing the processes of glycogenolysis(breakdown of glycogen) and gluconeogenesis(making glucose from other substrates). In addition to the effects of the four major glucose-controlling hormones, growth hormone increases mobilization of FFAs and decreases cellular uptake of glucose, so less glucose is used by the cells(more remains in circulation); and the thyroid hormones promote glucose catabolism and fat metabolism.

The amount of glucose released by the liver depends on exercise intensity and the duration. As intensity increases, so does the rate of catecholamine release. This can cause the liver to release more glucose than is being taken up by the active muscles. Consequently, during or shortly after an explosive, short-term sprint bout, blood glucose concentrations may be 40% to 50% above the resting level, illustrating that the glucose release by the liver is greater than the uptake by the muscles.

The greater the exercise intensity, the greater the catecholamine release, and thus the glycogenolysis rate is significantly increased. This process occurs not only in the liver but also in the muscle. The glucose released from the liver enters the blood to become available to the muscle. But the muscle has a more readily available source of glucose: its own glycogen. The muscle uses its own glycogen stores before using the plasma glucose during explosive, short-term exercise. Glucose released from the liver is not used as readily, so it remains in the circulation, elevating the plasma glucose. Following exercise, plasma glucose concentrations decrease as the glucose enters the muscle to replenish the depleted muscle glycogen stores.

During exercise bouts that last for several hours, however, the rate of liver glucose release more closely matches the muscles’ needs, keeping plasma glucose at or only slightly above the resting concentrations. As muscle uptake of glucose increases, the liver’s rate of glucose release also increases. In most cases, plasma glucose does not begin to decline until late in the activity as liver glycogen stores become depleted, at which time glucagons concentrations increase significantly. Glucagon and cortisol together enhance gluconeogenesis, providing more fuel.

Figure below illustrates the changes in plasma concentrations of epinephrine, norepinephrine, glucagon, cortisol, and glucose during 3h of cycling. Although the hormonal regulation of glucose remains intact throughout such longterm activities, the liver’s glycogen supply may become critically low. As a result, the liver’s rate of glucose release may be unable to keep pace with the muscles’ rate of glucose uptake. Under this condition, plasma glucose may decline despite strong hormonal stimulation. Glucose ingestion during the activity can play a major role in maintaining plasma glucose concentrations. 

Glucose uptake by muscle

Merely releasing sufficient amounts of glucose into the blood does not ensure that the muscle cells will have enough glucose to meet their energy demands. Not only must the glucose be released and delivered to these cells; it also must be taken up by the cells. Transport of glucose through the cell membranes and into muscle glucose through the cell membranes and into muscle cells in controlled by insulin. Once glucose is delivered to the muscle, insulin facilitates its transport into the fibers.

Surprisingly, as seen in figure below, plasma insulin concentration tends to decrease during prolonged submaximal exercise, despite a slight increase in plasma glucose concentration and glucose uptake by muscle. This apparent contradiction between the plasma insulin concentrations and the muscles’ need for glucose serves as a reminder that a hormone’s activity is determined not only by its concentration in the blood but also by a cell’s sensitivity to that hormone. Exercise may enhance insulin’s binding to receptors on the muscle fiber, thereby reducing the need for high concentrations of plasma insulin to transport glucose across the muscle cell membrane into the cell. This is important, because during exercise four hormones are trying to release glucose from its storage sites and create new glucose. High insulin concentrations would oppose their action, preventing this needed increase in plasma glucose supply. 

Regulation of fat metabolism during exercise

Although fat generally contributes less than carbohydrate to muscles’ energy needs during exercise, mobilization and oxidation of FFAs are critical to performance in endurance exercise. During such prolonged activity, carbohydrate reserves become depleted, and muscle must rely more heavily on the oxidation of fat for energy production. When carbohydrate reserves are low(low plasma glucose and low muscle glycogen), the endocrine system can accelerate the oxidation of fats(lypolysis), thus ensuring that muscles’ energy needs can be met.

Free fatty acids are stored as triglycerides in fat cells and inside muscle fibers. Adipose tissue triglycerides, however, must be broken down to release the FFAs, which are then transported to the muscle fibers. The rate of FFA uptake by active muscle correlates highly with the plasma FFA concentration. Increasing this concentration would increase cellular uptake of the FFA. The rate of triglyceride breakdown may determine, in part, the rate at which muscles use fat as a fuel source during exercise.

The rate of lypolysis is controlled by at least five hormones:

• (decreased) Insulin
• Epinephrine
• Norepinephrine
• Cortisol
• Growth hormone

The major factor responsible for adipose tissue lypolysis during exercise is a fall in circulating insulin. Lipolysis is also enhanced through the elevation of epinephrine and norepinephrine. In addition to having a role in gluconeogenesis, cortisol accelerates the mobilization and use of FFAs for energy during exercise. Plasma cortisol concentration peaks after 30 to 45 min of exercise and then decreases to near-normal levels. But the plasma FFA concentration continues to increase throughout the activity, meaning that lipase continues to be activated by other hormones. The hormones that continue this process are the catecholamines and growth hormone. The thyroid hormones also contribute to the mobilization and metabolism of FFAs, but to a much lesser degree.

Thus, the endocrine system plays a critical role in regulating ATP production during exercise as well as controlling the balance between carbohydrate and fat metabolism.

“Physiology of sport and exercise”, fourth edition; Jack H. Wilmore, David L. Costill, W. Larry Kenney