FACTORS ALTERING CONCENTRATION OF BLOOD LIPIDS 485 



show no abnormalities of blood cholesterol in patients with malignancies. 

 In fact, Guthmann, 824 De Voss 826 and Drevon 826 all noted that serum cho- 

 lesterol was decreased in cancer. No constant differences in blood cho- 

 lesterol were found in normal and in tumor-bearing rats, respectively. 313 - 827 



o. The Effect of Drugs on Blood Lipids, (a) Phlorhizin. Phlorhizin 

 is a glucoside obtained from the bark and root of the peach and pear tree 

 which, on hydrolysis, breaks down to glucose and phloretin. This sub- 

 stance is of interest in relation to blood lipids, since it acts on the kidneys 

 to produce glycosuria, with a subsequent ketosis and ketonuria. The 

 course of metabolism following daily injections of phlorhizin parallels that 

 which occurs in experimental pancreatic diabetes in the dog, or in diabetes 

 mellitus in man. In fact, the condition which obtains after an animal has 

 been "phlorhizinized" is referred to as "phlorhizin glycosuria" or "phlor- 

 hizin diabetes." This technic has been widely employed by the Lusk 

 school to determine what compounds are glucose formers. The results of 

 Deuel, Wilson, and Milhorat 828 and of Deuel alone 829 indicate that the 

 diabetic symptoms observed during phlorhizinization are to be traced to 

 carbohydrate depletion following the primary action of the drug on the 

 tubules of the kidneys. For a review of phlorhizin and glycosuria prior to 

 1912, the reader is referred to Lusk 830 ; Nash 831 contributed an excellent 

 review of the more recent work. See also Chapter II of this volume. 



Since the typical symptoms of phlorhizinized animals, especially when 

 fasted, resemble those of diabetes, one would also expect a hyperlipemia 

 to occur. This is actually the case, as has been proved by Lattes 221 as 

 well as by Terroine. 208 The latter worker reported that the level of both 

 fatty acids and cholesterol in the blood was increased after the drug was 

 given; moreover, the changes in each of these two lipid components pro- 

 ceeded independently. Allen 670 was unable to demonstrate a lipemia after 

 phlorhizin had been given; however, these discrepancies may well be due 

 to nutritional differences in the experimental animals, since the ketosis 

 and ketonuria disappear when the phlorhizinized dog receives more sugar 

 in the diet than it is physically able to eliminate. One would not expect 

 the animal to exhibit the diabetic symptoms of ketosis, ketonuria, or hyper- 



824 H. Guthmann, Arch. Gyndkol, 140, 202-225 (1930). 



825 G. De Voss, Z. physiol. Chem., 205, 20-24 (1932). 



826 B. Drevon, Compt. rend. soc. biol, 142, 974-977 (1948). 



827 F. Dannenberg, Biochem. Z., 244, 128-132 (1932). 



828 H. J. Deuel, Jr., H. E. C. Wilson, and A. T. Milhorat, J. Biol. Chem., 74, 265-298 

 (1927). 



829 H. J. Deuel, Jr., J. Biol Chem., 89, 77-91 (1930). 



830 G. Lusk, Ergeb. Physiol, 12, 315-392 (1912). 



831 T. P. Nash, Jr., Physiol. Revs., 7, 385-430 (1927). 



