The complicated theorizing of the von Noorden school, as represented by Falta's statements, found early acceptance among clinicians. However, there are many demonstrable errors in the presentation. Thus Ringer, in the experiments mentioned above, found no increase in the protein metabolism of his dogs after giving them epinephrin, and Lusk1 found the same to be true in normal dogs, and also discovered that if glucose were given to normal dogs and then epinephrin were administered the respiratory quotient rose to unity, showing a normal combustion of carbohydrate.

Fuchs and R6th2 state that the respiratory quotient increases in human beings after the subcutaneous injection of epinephrin, as appears below:

It is evident that the theory that epinephrin causes a production of sugar from fat, decreases the power of the organism to oxidize glucose through inhibition of pancreatic function, and stimulates the thyroid so that protein metabolism is increased, is untenable in any of its particulars.

In the matter of the thyroid being the cause of the high protein metabolism in diabetes, von.Noorden is right. Ep-pinger, Falta, and Rudinger3 extirpated both pancreas and thyroid and found that the protein metabolism was almost the same as in the normal dog instead of being increased three-or fourfold, as occurs when the pancreas alone is extirpated. The D : N ratio was at first 3.5, but declined after a few days to 2.8.

Von Noorden suggested to the writer of this book that the increased total metabolism which follows the administration of phlorhizin (see p. 474) would not take place if the thyroid gland had been previously extirpated. Lusk4 determined the metabolism of a dog after complete thyroidectomy with removal of three parathyroids and found it to be 19 calories per hour, whereas after phlorhizin administration values of 20.3 and 19.3 calories per hour were found, determined one and three days after diabetes had been induced. The usual rise in protein metabolism and total metabolism were absent. After the ingestion of meat, however, the heat production increased and rose on one occasion from a basal value of 17.5 to 26 calories per hour, an increase of 50 per cent. The urinary nitrogen largely increased and the process of amino-acid stimulation was in full play, notwithstanding the absence of the thyroid gland. This naturally suggests the hypothesis that the reason why there is no increased heat production in diabetes after thyroidectomy is that there is no rise in the quantity of protein metabolized.

1 Lusk: "Archives of Internal Medicine," 1914, xiii, 673.

2 Fuchs and R6th: "Zeitschrift fur ex. Path, und Ther.," 1912, x, 187.

3 Eppinger, Falta, and Rudinger: "Zeitschrift fur klinische Medizin," 1908, lxvi, 1.

4 Lusk: Proceedings of the XVIIth International Congress of Medicine, Section on Physiology, London, 1913, p. 13.

As shown by Parhon and by Cramer (see p. 442), thyroid ingestion causes the liver to discharge glycogen. Conversely, after thyroid extirpation the liver should retain glycogen more tenaciously than before. This, at least, would explain the. long continued high D : N ratios observed by Lusk in phlo-rhizinized dogs after thyroidectomy and by Miura1 in rabbits similarly treated.

In contradiction to the statements of Eppinger, Falta, and Rudinger, and of Miura, Underhill2 finds that epinephrin glycosuria may be as easily produced in thyroidectomized as in normal animals.

The subject of the correlation between the various glands of internal secretion is evidently one as replete with opportunities for the play of the imagination as it is for enlightening experimental research.

A question of special interest is the cause of the two D : N ratios, 2.8 : 1 and 3.65 :1. The former represents a production of 45 per cent., the latter one of 58 per cent, of sugar from meat protein. In neither case can ingested glucose be burned. It is, of course, possible that the sugar production varies under different circumstances; that is to say, the organism (liver?) may be able at times to produce sugar from a certain class of protein decomposition products, and at other times not. For example, it has been noted (p. 201) that glutamic acid is convertible into glucose in the dog, but Neuberg1 testifies that it may also be converted into butyric acid from which sugar cannot be formed. Or, one may adopt the hypothesis of Mandel and Lusk,2 which assumes a difference between α-colloid glucose and β-colloid glucose existing in the blood. By α-glucose is understood the amount of glucose represented by the ratio D : N : : 2.8 : 1, or 45 per cent, of the protein. The /3-glucose represents the additional 13.6 per cent, of the protein, when the ratio 3.65 :1 is present. The ratio would depend on the combustion or non-combustion of the /3-glucose. If the latter burns, it must do so as a complex, for as free glucose it would be eliminated in the urine.

1 Miura: "Biochemische Zeitschrift," 1913, li, 423.

2 Underhill: "American Journal of Physiology," 1910-ii, xxvii, 331.

This theory of a difference in chemical union would explain the fact discovered by Straub3 for carbon monoxid "diabetes" and by Seelig4 for glycosuria following ether inhalation, that sugar appears in the urine in large quantity if a dog be fed with meat, but disappears if the animal be given carbohydrate alone. Seelig found no glycosuria when an intravenous infusion of oxygen was administered at the same time that ether was given. It may be that lack of oxygen causes a dissociation of either a- or /3-colloid glucose derived from protein, which glucose then appears in the urine. This suggestion is, however, highly speculative.

1 Brasch and Neuberg: "Biochemische Zeitschrift," 1908, xiii, 299. 2 Mandel and Lusk: "Deutsches Archiv fur klinische Medizin," 1904, lxxxi, 491.

3 Straub: "Archiv fur exp. Path, und Pharm.," 1897, xxxviii, 139. 4 Seelig: Ibid., 1905, lii, 481.