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there is a very important objection to the view of its originating in the lungs. For, as has already been observed, the air entering the lungs must present the same amount of stimulating action throughout the whole day; and yet the result of that supposed action is found to vary at different times.
If, then, we are unprepared to relinquish entirely the idea of the intervention of nerve agency, and to suppose that the portal blood excites the secretion of sugar by a direct stimulating action upon the tissue of the liver, we must, in absence of a better explanation of the fact, adopt the opinion that the glucogenic function in a healthy animal, under ordinary circumstances, is called forth by the stimulating action of the portal blood upon the hepatic branches of the preumogastric nerves.
Since we now know that stimulants introduced into the portal circulation excite a flow of saccharine urine, we can easily understand how the excessive use of alcoholic drink may produce diabetes mellitus in individuals predisposed to the disease. The same fact explains to us how a disordered digestion is not unfrequently followed by saccharine urine. I may here relate a curious fact in illustration of the truth of the latter remark. About five years ago, at a time when I was much occupied in studying the physiology of diabetes, I regularly tested my urine twice a day, and on one occasion I found it to contain a small quantity of sugar. On the day in question I had partaken freely of asparagus salad ; and thinking that this might perhaps be the cause of the presence of sugar, I determined to try the effects of a greater quantity. The following day, the sugar having entirely disappeared from the urine, I again partook of the same salad both in the morning and afternoon. In the evening, on testing the urine, I found very distinct indications of sugar. As the observation was to me one of great interest, I determined to make some further experiments on the subject, in order to discover how many hours this state of saccharine urine would continue. During two days I ate large quantities of the asparagus salad, taking care to have it made as stimulating as possible with vinegar and pepper. The result was far beyond my expectations ; for instead of the sugar disappearing from the urine in a few hours after I had ceased partaking of the diet in question, it continued to be secreted during several days, until I at last became very much alarmed, lest the disease had been permanently induced. On the evening of the fourth day the sugar had almost entirely disappeared ; but on the fifth it returned in increased quantity—so much so, that a drop of urine falling on the boot left a distinct white spot. I could not account for the recurrence of the disease, as I had been particularly careful in my diet during the two previous days.
I have inentioned this experiment, because it appears to me that if a flow of saccharine urine be induced in a healthy person, as I consider myself to be, by disordering the digestion and over-exciting the liver, it is very probable that a cause insignificant in itself, but operating upon a predisposed constitution, might tend to produce the disease. Sugar in the urine has been found after eating cheese and other indigestible substances. It is worthy of remark, that Dr. Jessen, of Dorpat, has rendered horses diabetic by feeding them with hay damaged by moisture. M. Leconte has also found sugar in the urine of dogs after he had administered to them the nitrate of uranium. Several other substances have the same effect, and I have no doubt but that a great number more stimulants will be afterwards found to produce similar results. I cannot refrain from mentioning with what pleasure I perused a communication of M. Bernard's, entitled, On the Influence of Alcohol and Ether on the Secretions of the Digestive Canal, of the Pancreas, and of the Liver, read before the Société de Biologie. * M. Bernard, instead of putting the alcohol and ether, as I had done, directly into the portal vein, introduced them, by means of a long @sophagus tube, into the duodenum of dogs, and allowed them to be absorbed through the walls of the intestine into the portal circulation. The result, as might à priori have been anticipated, was identical with what I had previously obtained. M. Bernard, in fact, found that six cubic centimètres of alcohol mixed with an equal amount of water was sufficient to excite the liver to secrete a large quantity of sugar, even while the animal was fasting. With ether employed in a similar manner, he obtained no less successful results. It would be very interesting and important to ascertain if the simple introduction of alcohol into the stomach would produce the same effect. It is possible that in some cases it might fail to do so, on account of its being so acted upon by the gastric juice that it had lost its stimulating properties before it reached the portal circulation. The experiment is, however, one worth making, as in many works on diabetes, drunkards are said to be peculiarly liable to the disease. +
Having thus briefly considered some of the more important facts connected with the exciting cause of the glucogenic function of the liver, I shall conclude with a few remarks on the destruction of the sugar in the animal economy.
In the early part of last year, M. Chauveau communicated to the French Academy a very interesting memoir upon the destruction of sugar in the animal body. His experiments, which seem to have been most carefully executed, were made on the blood drawn from the arteries and corresponding veins of horses, donkeys, and dogs. And from the results which he obtained he concludes—firstly, that the sugar is not destroyed in any appreciable quantity during its passage through the lungs; and, secondly, that a certain amount of saccharine matter disappears in its passage through the capillaries of the general circulation. I have repeated M. Chauveau's experiments on the dog, and have made some others on the cat, and the results obtained are confirmatory of the conclusions arrived at by that gentleman,
The result of the following experiment upon a dog shows that the blood loses very little of its sugar during its passage through the lungs. In order to obtain the blood from the right side of the heart, I followed the method adopted by Messrs. Bernard and Chauvean. The external jugular vein on the right side of the neck was separated for
. Gazette Médicale de Paris, Mai 10, 1856. † Some interesting remarks upon the effects of diet are to be found in Dr. Garrod's Gulstonian Lectures. See British Medical Journal, April 18th, 1857.
about an inch in extent from the neighbouring tissues, and a ligature placed on the vessel as high up as possible, to prevent the return of the blood from the head through this channel. An opening was then made in the vein immediately below the ligature, and a flexible catheter passed through it down into the right auricle. A portion of venous blood was now withdrawn from the heart by means of a syringe attached to the free end of the catheter. This blood of course contained the saccharine matter which had been poured out by the liver into the inferior vena cava. The blood from the left side of the heart was readily obtained by puncturing the carotid artery.
The manner in which I determined the amount of sugar in these portions of blood was the following: A quantity of distilled water, equal to four times that of the blood, was boiled in a capsule. To the water, when boiling, were added a couple of drops of acetic acid, and afterwards the blood was very gradually introduced. In order that the albumen might be thoroughly coagulated, a drop or two more of the acetic acid was added, care being, however, taken to avoid an excess. When the albumen was completely coagulated, which was known by its separating and floating in the then clear liquid, it was filtered. '(I think this is preferable to Bernard's method of decolorizing the blood by means of sulphate of soda, and it is equally applicable when operating on the solid tissues - the liver, for example.) The sugar in the clear filtered liquid was calculated by means of Fehling's standard solution of sulphate of copper. The blood from the right side of the heart was found to contain 0.100 per cent. of saccharine matter, while that from the left side of the heart contained 0·085 per cent. The small quantity of sugar in the blood is easily accounted for by the animals having fasted about fifteen hours previous to the withdrawal of the blood. This result shows that very little sugar had been transformed during its passage through the lungs.
In another experiment which I performed on a cat* in an exactly similar manner, I found that the blood of the right side of the heart contained 0.18 per cent. of sugar, and that from the left an exactly similar amount. In order to be certain that I had made no mistake in the determination of the sugar by the volumetric method, I carefully collected the reduced oxide of copper dried, and weighed it. The amount of precipitate from both bloods was identical, thus confirming the result obtained by the volumetric method. I may here mention that Chauveau on one occasion found more sugar in the blood after than before its passage through the lungs. I also obtained a similar result, but was fortunate enough, however, to find that it depended upon the position of the end of the catheter when withdrawing the blood from the right side of the heart. The result, therefore, is of no value, either for or against the theory of the pulmonary destruction of sugar.
Being still occupied with this subject, I refrain at present from entering more iuto detail, or quoting other experiments in confirmation of the conclusions drawn from the above observations.
It is almost superfluous to state that the results of these experiments * I had no means of knowing how long this animal had fasted. On killing him after I had obtained the blood, I found the stornach empty.
fully confirm the conclusion arrived at by M. Chauveau, that the sugar is not destroyed in any appreciable quantity during its passage through the lungs. This indeed appears to ine what might have been anticipated when the true nature of the pulmonary function is considered. For what are the lungs? They are not laboratories, like the stomach, but merely an aggregation of little thin sacs, whose function is purely physical; at least, in as far as respiration is concerned. The only “ vital" offices which they perform are simply those required for their own development and preservation. The mere absorption of oxygen and exhalation of carbonic acid gas would perhaps go on just in the same manner if a piece of goldbeater's skin occupied the place of the lungs. We now smile at Lavoisier's idea regarding the absorbed oxygen entering into immediate combination with the free carbon supposed to exist in the lungs for the formation of carbonic acid gas, and perhaps the next generation may with equal right ridicule the present idea of the combustion or fermentation of sugar in the lungs. Formerly it was believed, too, that the bile was burned in the lungs in order to keep up the animal heat; but this theory has been laid aside since the lungs were found to be the least warm of the internal organs. The blood takes but a second or two to pass through the lungs; so that if the saccharine matter is transformed in these organs, the process of transformation must be almost instantaneous. Granting that it is so, why, we ask, does the decomposition of the sugar take place in the lungs alone? We know that the presence of oxygen is not necessary for the transformation; and even if it were, abundance of that gas is to be found in the general circulation. It has been said that the presence of fibrin is necessary for the decomposition of sugar : if it is, are the lungs the only source of fibrin, or is the fibrin circulating in the capillaries of the pulmonary organs different from that in the capillaries of the rest of the body? Chemistry has as yet failed to detect any difference; and as there is plenty of oxygen as well as fibrin in the general circulation, I can see no reason why the transformation of saccharine matter should be entirely performed in one organ of the body. If Bernart is right in saying that the whole sugar is decomposed by the lungs there must exist in these organs a something possessing the specific property alluded to. Are there any peculiar cells in the tissue of lung which secrete a substance capable of transforming the saccharine mattert I am well aware that Verdeil discovered an acid in the polmonary tissue to which he gave the name of pneumic acid, and that Bernari imagined it pissible that this substance might bave the power of transforming the sugar in its passage through the lungs; but this was only a pagne hrpothesis without any evidence to support it. Pneumie acid was not known to have the property of decomposing
gain, it might be askeri, Are there any peculiar cells in the walls of the pulmonary asillaries which have the magical power of transforming the sugar as it is rapidly carried past! Or does the blood,
• Pri sta, urteroch, das found unie acid to be a pardaet of decomposition, an
arriving at the lungs for the purpose of arterialization, leave the capillaries to become in any way incorporated with their tissue? No positive answer can be found to either question. Where, then, is a single proof of the destruction of saccharine matter occurring in the respiratory organs? except that Bernard found large quantities of sugar on the right, and very small quantities on the left side of the heart, and has been supported in this view by Dr. Pavy. Chauveau, on the other hand, has shown that carefully-executed experiments give an opposite result; in which opinion the conclusions drawn from my own investigations lead me entirely to coincide.
Having made these few remarks upon the probability or non-pro. bability of the sugar being destroyed in the lungs, we now take a cursory glance at what may be called the opposite side of the question. Does the saccharine matter disappear in the capillaries of the general circulation ? This question has been answered in the affirmative by M. Chauveau, who found that blood drawn from a vein contained less sugar than that taken from the corresponding artery. I may here very briefly quote one of my own experiments in confirmation of this statement. I took from the femoral artery of a middle-sized dog, four hours after he had been fed with animal food, one ounce of blood, and from the corresponding vein an exactly similar quantity. On analyzing these bloods, I found the arterial to contain 0-24 per cent., while the venous blood contained only 0.16 per cent, of saccharine matter. This fact seems to be supported by analogy, when the probable uses of sugar in the animal body are taken into consideration. We now know, for example, that all animals, from a very early period of their development in the uterus up to the time of their maturity and decay, have a sugargenerating apparatus in more or less active operation. We know that daily and hourly, so long as the liver remains in a normal condition, it is manufacturing saccharine matter from the ingesta, be they animal or vegetable. We further know that during digestion, when the blood is loaded with nutritive materials, and when, consequently, the assimilative process is looked upon as being most active, the greatest amount of sugar is thrown into the general circulation. These and similar facts clearly indicate that sugar must play an important part in the nutritive process, and almost force us to believe that, like the other nutritive materials poured into the blood, it furnishes to the different tissues and organs some of the substances necessary for their development and repair. Not only am I disinclined to admit that sugar is supplied to the body for the purpose of keeping up the animal heat, but I am even loth to believe that any individual substance is taken into the system solely for that purpose. On the contrary, the production of animal heat ray be regarded as a matter of secondary importance, and simply as the necessary result of the chemical changes which occur during the metamorphosis of the tissues.
If, then, the sugar formed by the liver goes to the support of the system, it is easy to understand how it should disappear from the general circulation during its transit through the minute capillaries of the different tissues. It will, in fact, leave the blood vessels, to be trans