Bodily changes in pain, hunger, fear, and rage

by Walter B. Cannon

The Question Whether Adrenin Normally Secreted Inhibits the Use of Sugar in the Body

The only evidence opposed to the conclusion which has just been drawn is that which may be found in results recently reported by Wilenko. He injected adrenin into urethanized rabbits, usually one milligram per kilo body weight, and then found that the animals did not oxidize any part of an intravenous injection of glucose. Rabbits supplied with glucose in a similar manner, but not given adrenin, have an increased respiratory quotient. Wilenko[23] concluded, therefore, that adrenin lessens the capacity of the organism to burn carbohydrates. In a later paper he reported that adrenin, when added, with glucose, to physiological salt solution (Locke’s), and perfused through the isolated rabbit heart, notably increases the use of sugar by the heart (from 2.2–2.8 to 2.9–4.3 milligrams of glucose per gram of heart muscle per hour), but that the heart removed after the animal has received a subcutaneous injection of adrenin uses much less sugar, only 0.5–1.2 milligrams per gram per hour. From these results Wilenko[24] concludes that the glycosuria following injection of adrenin is the result of disturbance of the use of sugar—an effect which is not direct on the sugar-consuming organ, but indirect through action on some other organ.

Wilenko’s conclusion fails to account readily for the disappearance of glycogen from the liver in adrenin glycosuria. Furthermore, Lusk[25] has recently reported that the subcutaneous administration of adrenin (one milligram per kilo body weight) to dogs, simultaneously with 50 grams of glucose by mouth, interferes not at all with the use of the sugar—the respiratory quotient remains for several hours at 1.0; i. e., at the figure which glucose alone would have given. In other words, Lusk’s results with dogs are directly contradictory to Wilenko’s results with rabbits. Nevertheless, Wilenko’s conclusion might be quite true for the glycosuria produced by adrenin alone (which must be excessive), and yet have no bearing whatever on the glycosuria produced physiologically by splanchnic stimulation, even though some adrenin is thereby simultaneously liberated.

The amount of injected adrenin used to produce adrenin glycosuria is enormous. Osgood has studied in the Harvard Physiological Laboratory the effects on blood pressure of alternately stimulating the left splanchnic nerves (with the splanchnic vessels eliminated) and injecting adrenin, and by this method of comparison[26] has shown that the amount secreted after five seconds of stimulation varies between 0.0015 and 0.007 milligram. If 0.005 milligram is taken as a rather high average figure, and doubled (for two glands), the amount would be 0.01 milligram. To produce adrenin glycosuria, an animal weighing two kilos would be injected with two hundred times this amount. It is granted that more adrenin would be secreted if the nerves were stimulated longer than five seconds, and that with injection under the skin or into the abdominal cavity (to produce glycosuria), the amount of adrenin in the blood at one time would not be so great as if the injection were into a vein; but even with these concessions the amount of adrenin in the blood, when it has been injected to produce glycosuria, is probably very much above the amount following physiological stimulation of the glands.

Other evidence that the amount of adrenin discharged when the glands are stimulated is not so great as the amount needed to produce glycosuria when acting alone is presented in experiments by Macleod.[27] He found that if the nerve fibres to the liver were destroyed, stimulation of the splanchnic, which would cause increased adrenal secretion, did not increase the blood sugar. The increased blood sugar due to splanchnic stimulation, therefore, is a nervous effect, dependent, to be sure, on the presence of adrenin in the blood, but the amount of adrenin present is not in itself capable of evoking increase.

Furthermore, the increased blood sugar following splanchnic stimulation may long outlast the stimulation period. The adrenals, however, as has been demonstrated by Osgood, are soon fatigued, and fail to respond to repeated stimulation. They seem to be incapable of prolonged action.

Again, as Macleod[28] has shown, a rise in the sugar content of the blood can be induced, if the adrenals are intact, merely by stimulating the nerves going to the liver. The increased blood sugar of splanchnic origin, therefore, is not due to a disturbance of the use of sugar in the body, as Wilenko claims for the increase after adrenin injection, but is a result of a breaking down of the stored glycogen in the liver and is of nervous origin.

We may conclude, therefore, that since the conditions of Wilenko’s observations are not comparable with emotional conditions, his inferences are not pertinent to the present discussion; that when both adrenin and sugar are increased in the blood as a result of excitement, the higher percentage of sugar is not due to adrenin inhibiting the use of sugar by the tissues, and that there is no evidence at present to show that the brief augmentation of adrenal discharge, following excitement or splanchnic stimulation, affects in any deleterious manner the utilization of sugar as a source of energy. Indeed, the observation of Wilenko and of Patterson and Starling, above mentioned, that adrenin increases the use of sugar by the heart, may signify that a physiological discharge of the adrenals can have a favorable rather than an unfavorable effect on the employment of sugar by the tissues.