Hormonal Interactions During Exercise

During exercise, overall oxygen consumption may increase 10-15 times in a well-trained young athlete. The requirements for fuel are met by mobilization of reserves within muscle cells and from extramuscular fuel depots. Rapid uptake of glucose from blood can potentially deplete, or at least dangerously lower, glucose concentrations and hence jeopardize the brain unless some physiologic controls are operative. We can consider two forms of exercise: short-term maximal effort, characterized by sprinting for a few seconds, and sustained aerobic work, characterized by marathon running.

Short-Term Maximal Effort

For the few seconds of the 100-yard dash, endogenous ATP reserves in muscle, creatine phosphate and glycogen, are the chief sources of energy. For short-term maximal effort, energy must be released from fuel before circulatory adjustments can provide the required oxygen. Breakdown of glycogen to lactate provides the needed ATP and is activated in part through intrinsic biochemical mechanisms that activate glycogen phos-phorylase and phosphofructokinase. For example, calcium released from the sarcoplasmic reticulum in response to neural stimulation not only triggers muscle contraction but also activates glycogen phosphorylase. These intrinsic mechanisms are reinforced by epinephr-ine and norepinephrine released from the adrenal medullae and sympathetic nerve endings in response to central activation of the sympathetic nervous system.

The endocrine system is important primarily for maintaining or replenishing fuel reserves in muscle. Through the actions of hormones and the glucose-fatty acid cycle already discussed, glycogen reserves in muscle are sustained at or near capacity, so that muscle is always prepared to respond to demands for maximal effort. During the recovery phase lactate released from working muscles is converted to glucose in liver and can be exported back to muscle in the classic Cori cycle. Insulin secreted in response to increased dietary intake of glucose or amino acids promotes reformation of glycogen.

Sustained Aerobic Exercise

Glucose taken up from the blood or derived from muscle glycogen is also the most important fuel in the early stages of moderately intense exercise, but with continued effort dependence on fatty acids increases. Although fat is a more efficient fuel than glucose from a storage point of view, glucose is more efficient than fatty acids from the perspective of oxygen consumption and yields about 5% more energy per liter of oxygen. Table 5 shows the changes in fuel consumption with time in subjects exercising at 30% of their maximal oxygen consumption. For reasons that are not fully understood,

3 4 Days

FIGURE 9 Concentrations of glucose in the plasma of normal subjects (Control) and patients suffering from isolated deficiency of GH (shown in blue) while eating normally and while fasting. Some GH-deficient patients were untreated while others were given 5 mg of human GH per day (treated). Fasting began after collection of blood on day 2. From Merimee, TJ, Felig, P, Marliss, E, Fineberg, SE, Cahill, GF Jr. (1971). Glucose and lipid homeostasis in absence of human growth hormone. J. Clin. Invest. 50:574-582. With permission.

working muscles, even in the trained athlete, cannot derive more than about 70% of their energy from oxidation of fat. Hypoglycemia and exhaustion occur when muscle glycogen is depleted. With sustained exercise, the decline in insulin and the increase in all of the counter-regulatory hormones contribute to supplying fat to the working muscles and maximizing gluconeogenesis (Fig. 10).

Anticipation of exercise may be sufficient to activate the sympathetic nervous system, which is of critical importance not only for supplying the fuel for the working muscles but for making the cardiovascular adjustments that maintain blood flow to carry fuel and oxygen to muscle, gluconeogenic precursors to liver, and heat to sites of dissipation. Insulin secretion is shut down by sympathetic activity. This removes the major inhibitory influence on production of glucose by the liver,

TABLE 5 Fuels Consumed by Leg Muscles of Man during Mild Prolonged Exercise

%Contribution to oxygen uptake

Period of


Plasma free




fatty acids


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