520 TEXT-BOOK OF PHYSIOLOGY 



It is assumed by the supporters of the second view that the production 

 of sugar in the liver cells is regulated by two opposing factors or hormones, 

 that secreted by the adrenal glands and that secreted by the pancreas, the 

 former exciting, the latter inhibiting the process. In the absence of the 

 pancreatic hormone the adrenal hormone unduly excites the production of 

 sugar. The following facts support this view: After extirpation of the adre- 

 nals or ligation of the adrenal veins, by which the secretion is prevented from 

 entering the venous blood, the removal of the pancreas is not followed as 

 usual by glycosuria. The simultaneous injection of an extract of pancreas 

 and an injection of that amount of adrenalin ordinarily necessary to produce 

 glycosuria prevents its development. 



Pharmacologic Glycosuria. It is well known that various pharmacologic 

 agents when introduced into the body frequently give rise to glycosuria, 

 though the manner in which they do so is not always clear. Thus, the ad- 

 ministration of ether, curare, the uranium salts, phlorhizin, etc., is generally 

 followed by the elimination of sugar in varying amounts. Of these agents 

 the one generally used for experimental purposes is: 



Phlorhizin. Phlorhizin is a glucosid obtained from the root bark of the 

 cherry, plum and apple tree. It can readily be separated into glucose and 

 phloretin on the latter of which its action depends. If, therefore, either 

 phlorhizin or phloretin be injected subcutaneously or administered by the 

 mouth, sugar very promptly will appear in the urine in amounts varying, 

 with the dosage, from 5 to 15 per cent. This glycosuria is, however, tem- 

 porary, but may be made more or less continuous by repeated injections at 

 least three or four times daily. Coincidently there is a diminution in the 

 percentage of sugar in the blood (hypoglycemia), the opposite condition to 

 that observed in the glycosurias heretofore mentioned. Inasmuch as this 

 deficiency calls for a larger discharge of sugar from the liver this organ and 

 others as well, soon become free from glycogen especially if the animal be 

 deprived of carbohydrate food. Experimental investigations lead to the con- 

 clusion that the seat of action of the phlorhizin is in the kidney itself (whether 

 in the glomerular or in the renal epithelium is uncertain) , in consequence of 

 which the sugar of the blood is permitted to pass along with other constitu- 

 ents into the tubules and hence into the urine. As to the change which the 

 kidney structures undergo under the action of phlorhizin not nruch is known. 

 It has been assumed that ordinarily the sugar is in combination with colloid 

 material in the blood and by reason of this combination cannot pass across 

 the wall of the glomerular blood-vessels. Any uncombined sugar, as is the 

 case in hyperglycemia, will diffuse readily in the urine. Under the influence 

 of phlorhizin the kidney structure is presumed to acquire the power of break- 

 ing up this combination setting the sugar free, whereupon it at once diffuses 

 into the urine. When phlorhizin is administered to an animal living on a 

 meat and fat diet alone, after all sugar has been discharged from the body, 

 sugar still appears in the urine indicating that it must have some other origin 

 than the glycogen of the liver or other tissues. The ratio of the dextrose to 

 the nitrogen in the urine 2.8 to i (Minkowski) or 3.65 to i (Lusk), a ratio 

 which corresponds to that found in the urine of diabetic patients living on a 

 meat-fat diet, leads to the conclusion that the sugar arises from the metabo- 

 lism of protein in a mariner already alluded to. 



Pituitary Glycosuria. It was discovered by Gushing during his experi- 



