After Blum's discovery of the production of glycosuria by the subcutaneous injection of adrenal extract, Herter has the merit of having found that injection of adrenalin into the peritoneal cavity also produces glycosuria; this is an undeniable fact. Concerning Herter's claim that intraperitoneal injection gives a higher degree of glycosuria than subcutaneous or intravenous injection, we offer no comment since we have made no observations on the glycosuric effect of subcutaneous injection of adrenalin, while we have made only three experiments by intraperitoneal injection. The most we can predicate on the basis of the present experiments is that intraperitoneal injection of adrenalin produces a somewhat higher degree of glycosuria than could be anticipated. However, in an earlier study carried out several years ago we arrived at the conception that the more slowly adrenalin was absorbed from the tissues into the circulation, the greater was its glycosuric effect; hence an intramuscular injection, which in its effect is nearly equal to that of an intravenous injection, induced a glycosuria definitely smaller than that set up by a similar dose administered subcutaneously. Unless the absorption from the peritoneal cavity is shown to be different from the absorption from subcutaneous injections, there could be no reason to assume that the glycosuric effect of intraperitoneal injection is much greater than that of subcutaneous injection. We might add that our former experiments do not support Herter's view that subcutaneous injection of adrenalin yields only slight degrees of glycosuria, because it is largely oxidized before entering the circulation. A difference exists in the effects upon blood pressure and upon sugar production, depending upon the mode of administration of adrenalin. With regard to the sugar production, a subcutaneous injection has a definitely greater effect than an intravenous injection; with regard to the blood pressure effect, however, the opposite is true. Herter states that an intraperitoneal injection of adrenalin exerts a smaller effect upon blood pressure than an intravenous injection—a fact which Auer and Meltzer can confirm for the rabbit.
Our experiments lead us to conclusions which do not conform to those of Herter. It will be recalled that Herter and his coworkers state first, that painting the pancreas causes a marked glycosuria and hyperglycemia, and, second, that the glycosuria and hyperglycemia produced by intraperitoneal injections are of pancreatic origin; that is, they are produced by the adrenalin's coming in contact with the pancreas. In our experiments tabulated in Table IV, in which the pancreas was isolated from the rest of the peritoneal cavity, the glycosuria was about one-third, and the rise in blood sugar about two-thirds that obtained by painting the unisolated pancreas. Hence two facts may be deduced: first, that the painting of the isolated pancreas produces only mild glycosuria and hyperglycemia, and, second, that the greater production of sugar observed after the painting of the unisolated pancreas cannot be of pancreatic origin. Indeed, our experiments point rather to the conclusion that the larger production of sugar after painting the unisolated pancreas is due to the fact that a large part of the adrenalin escapes to the peritoneum. The last mentioned view is supported by the statement of Herter and Wakeman that "applications to the kidney are apt to yield more sugar than similar application to the liver, intestine, spleen, or brain, but the glycosuria is less marked than after the pancreas has been painted." Emerson and one of us had shown that a dissolved substance painted upon a kidney with an intact membrane is incapable of penetrating the membrane and affecting the kidney, or even incapable of entering the circulation, except when the solution escapes to other parts of the peritoneum. It was this observation which led to the suggestion that the effects observed by Herter of painting the pancreas might have been due to the escape of adrenalin to the celiac ganglion. This point has not been directly tested, but several experiments were performed in which the adrenals were painted with the effect on sugar production apparently as intense as that obtained by painting the unisolated pancreas. However this may be, and whether the production of sugar after painting the unisolated pancreas is due to the escape of adrenalin to some definite organ covered by the peritoneum (celiac ganglion or adrenals) or whether the peritoneum as a whole is responsible for the sugar production, it appears that, when sugar production follows the intraperitoneal injection of adrenalin, it is not of pancreatic origin.