urine has often appeared to be altogether out of proportion to that which could be accounted for by the vegetable substances taken as food. The experiments of Bernard, the most important of which we have repeatedly confirmed, in common with other investigators, show that in these instances most of the sugar has an internal origin, and that it first makes its appearance in the tissue of the liver.

If a carnivorous animal, as, for example, a dog or a cat, be fed for several days exclusively upon meat, and then killed, the liver alone of all the internal organs is found to contain sugar among its other ingredients. For this purpose, a portion of the organ should be cut into small pieces, reduced to a pulp by grinding in a mortar with a little water, and the mixture coagulated by boiling with an excess of sulphate of soda, in order to precipitate the albuminous and coloring matters. The filtered fluid will then reduce the oxide of copper, with great readiness, on the application of Trommer's test. A decoction of the same tissue, mixed with a little yeast, will also give rise to fermentation, producing alcohol and carbonic acid, as is usual with saccharine solutions. On the contrary, the tissues of the spleen, the kidneys, the lungs, the muscles, &c., treated in the same way, give no indication of sugar, and do not reduce the salts of copper. Every other organ in the body may be entirely destitute of sugar, but the liver always contains it in considerable quantity, provided the animal be healthy. Even the blood of the portal vein, examined by a similar process, contains no saccharine element. and yet the tissue of the organ supplied by it shows an abundance of saccharine ingredients.

It is remarkable for how long a time the liver will continue to exhibit the presence of sugar, after all external supplies of this substance have been cut off. Bernard kept two dogs under his own. observation, one for a period of three, the other of eight months,' during which period they were confined strictly to a diet of animal food (boiled calves' heads and tripe), and then killed. Upon examination, the liver was found, in each instance, to contain a proportion of sugar fully equal to that present in the organ under ordinary circumstances.

The sugar, therefore, which is found in the liver after death, is a normal ingredient of the hepatic tissue. It is not formed in other parts of the body, nor absorbed from the intestinal canal, but takes

Nouvelle Fonction du Foie, p. 50.

its origin in the liver itself; it is produced, as a new formation, by a secreting process in the tissue of the organ.

The presence of sugar in the liver is common to all species of animals, so far as is yet known. Bernard found it invariably in monkeys, dogs, cats, rabbits, the horse, the ox, the goat, the sheep, in birds, in reptiles, and in most kinds of fish. It was only in two species of fish, viz., the eel and the ray (Muræna anguilla and Raia batis), that he sometimes failed to discover it; but the failure in these instances was apparently owing to the commencing putrescence of the tissue, by which the sugar had probably been destroyed. In the fresh liver of the human subject, examined after death from accidental violence, sugar was found to be present in the proportion of 1.10 to 2.14 per cent. of the entire weight of the organ.

The following list shows the average percentage of sugar present in the healthy liver of man and different species of animals, according to the examinations of Bernard :

With regard to the nature and properties of the liver sugar, it resembles very closely glucose, or the sugar of starch, the sugar of honey, and the sugar of milk, though it is not absolutely identical with either one of them. Its solution reduces, as we have seen, the salts of copper in Trommer's test, and becomes colored brown when boiled with caustic potass. It ferments very readily, also, when mixed with yeast and kept at the temperature of 70° to 100° F. It is distinguished from all the other sugars, according to Bernard,' by the readiness with which it becomes decomposed in the bloodsince cane sugar and beet root sugar, if injected into the circulation of a living animal, pass through the system without sensible decomposition, and are discharged unchanged with the urine; sugar of milk and glucose, if injected in moderate quantity, are decomposed in the blood, but if introduced in greater abundance make their appearance also in the urine; while a solution of liver sugar, though injected in much larger quantity than either of the others, may dis

'Leçons de Physiologie Expérimentale. Paris, 1855, p. 213.

appear altogether in the circulation, without passing off by the kidneys.

This substance is therefore a sugar of animal origin, similar in its properties to other varieties of saccharine matter, derived from different sources.

The sugar of the liver is not produced in the blood by a direct decomposition of the elements of the circulating fluid in the vessels of the organ, but takes its origin in the solid substance of the hepatic tissue, as a natural ingredient of its organic texture. The blood which may be pressed out from a liver recently extracted from the body, it is true, contains sugar; but this sugar it has absorbed from the tissues of the organ in which it circulates. This is demonstrated by the singular fact that the fresh liver of a recently killed animal, though it may be entirely drained of blood and of the sugar which it contained at the moment of death, will still continue for a certain time to produce a saccharine substance. If such a liver be injected with water by the portal vein, and all the blood contained in its vessels washed out by the stream, the water which escapes by the hepatic vein will still be found to contain sugar. M. Bernard has found' that if all the sugar contained in a fresh liver be extracted in this manner by a prolonged watery injection, so that neither the water which escapes by the hepatic vein, nor the substance of the liver itself, contain any further traces of sugar, and if the organ be then laid aside for twenty-four hours, both the tissue of the liver and the fluid which exudes from it will be found at the end of that time to have again become highly saccharine. The sugar, therefore, is evidently not produced in the blood circulating through the liver, but in the substance of the organ itself. Once having originated in the hepatic tissue, it is absorbed thence by the blood, and transported by the circulation, as we shall hereafter show, to other parts of the body.

The sugar which thus originates in the tissue of the liver, is produced by a mutual decomposition and transformation of various other ingredients of the hepatic substance; these chemical changes being a part of the nutritive processes by which the tissue of the organ is constantly sustained and nourished. There is probably a series of several different transformations which take place in this manner, the details of which are not yet known to us. It has been discovered, however, that one change at least precedes the final

'Gazette Hebdomadaire, Paris, Oct. 5, 1855.

production of saccharine matter; and that the sugar itself is produced by the transformation of another peculiar substance, of anterior formation. This substance, which precedes the formation of sugar, and which is itself produced in the tissue of the liver, is known by the name of the glycogenic matter, or glycogene.

This glycogenic matter may be extracted from the liver in the following manner. The organ is taken immediately from the body of the recently killed animal, cut into small pieces, and coagulated by being placed for a few minutes in boiling water. This is in order to prevent the albuminous liquids of the organ from acting upon the glycogenic matter and decomposing it at a medium temperature. The coagulated tissue is then drained, placed in a mortar, reduced to a pulp by bruising and grinding, and afterward boiled in distilled water for a quarter of an hour or more, by which the glycogenic matter is extracted and held in solution by the boiling water.

The liquid of decoction, which should be as concentrated as possible, must then be expressed, strained, and filtered, after which it appears as a strongly opalescent fluid, of a slightly yellowish tinge. The glycogenic matter which is held in solution may be precipitated by the addition to the filtered fluid of five times its volume of alcohol. The precipitate, after being repeatedly washed with alcohol in order to remove sugar and biliary matters, may then be redissolved in distilled water. It may be precipitated from its watery solution either by alcohol in excess or by crystallizable acetic acid, in both of which it is entirely insoluble, and may be afterward kept in the dry state for an indefinite time without losing its properties.

The glycogenic matter, obtained in this way, is regarded as intermediate in its nature and properties between hydrated starch and dextrine. Its ultimate composition, according to M. Pelouze,' is as follows:

C12H2012

When brought into contact with iodine, it produces a coloration varying from violet to a deep, clear, maroon red. It does not reduce the salts of copper in Trommer's test, nor does it ferment when placed in contact with yeast at the proper temperature. It does not, therefore, of itself contain sugar. It may easily be converted into sugar, however, by contact with any of the animal ferments, as, for example, those contained in the saliva or in the

'Journal de Physiologie, Paris, 1858, p. 552.

blood. If a solution of glycogenic matter be mixed with fresh human saliva, and kept for a few minutes at the temperature of 100° F., the mixture will then be found to have acquired the power of reducing the salts of copper and of entering into fermentation by contact with yeast. The glycogenic matter has therefore been converted into sugar by a process of catalysis, in the same manner as vegetable starch would be transformed under similar conditions. The glycogenic matter which is thus destined to be converted into sugar, is formed in the liver by the processes of nutrition. It may be extracted, as we have seen above, from the hepatic tissue of carnivorous animals, and is equally present when they have been exclusively confined for many days to a meat diet. It is not introduced with the food; for the fleshy meat of the herbivora does not contain it in appreciable quantity, though these animals so constantly take starchy substances with their food. In them, the starchy matters are transformed into sugar by digestion, and the sugar so produced is rapidly destroyed after entering the circulation; so that usually neither saccharine nor starchy substances are to be discovered in the muscular tissue. M. Poggiale' found that in very many experiments, performed by a commission of the French Academy for the purpose of examining this subject, glycogenic matter was detected in ordinary butcher's meat only once. We have also found it to be absent from the fresh meat of the bullock's heart, when examined in the manner described above. Nevertheless, in dogs fed exclusively upon this food for eight days, glycogenic matter may be found in abundance in the liver, while it does not exist in other parts of the body, as the spleen, kidney, lungs, &c.

Furthermore, in a dog fed exclusively for eight days upon the fresh meat of the bullock's heart, and then killed four hours after a meal of the same food, at which time intestinal absorption is going on in full vigor, the liver contains, as above mentioned, both glycogenic matter and sugar; but neither sugar nor glycogenic matter can be found in the blood of the portal vein, when subjected to a similar examination.

The glycogenic matter, accordingly, does not originate from any external source, but is formed in the tissue of the liver; where it is soon afterward transformed into sugar, while still forming a part of the substance of the organ.

' Journal de Physiologie, Paris, 1858, p. 558.