192 II. DIGESTION AND ABSORPTION OP FATS 



Iii addition, half of the fat in the intestine was found to be in the form of 

 fatty acids, in the case of monoiodoacetate-treated rats. 



On the other hand, the studies with monoiodoacetate were criticized 

 by Klinghoffer 761 and by Ohnell and Hober, 762 on the grounds that this sub- 

 stance is very toxic and produces bleeding and irreversible damage to the 

 intestinal mucosa. It was pointed out that the animals subjected to iodo- 

 acetate also presented a decrease in the absorption of NaCl, as well as of 

 xylose and of the hexoses. Although the decreased absorption of hexoses 

 is in agreement with the theory of Verzar that monoiodoacetate inhibits 

 phosphorylation (and hence prevents absorption of hexoses), one is unable 

 to answer the other criticisms on this basis. 



b. Phlorhizin. Verzar and Laszt 861 were the first to report that inhibi- 

 tion of fat absorption was brought about by the injection of the glucoside, 

 phlorhizin. This substance was shown by von Mering, 862 in 1886, to 

 produce an intense glycosuria; however, the polyuria resulting from this 

 compound is reversible, inasmuch as it ceases as soon as phlorhizin has been 

 eliminated from the system. 



Phlorhizin (also spelled phlorhidzin, phlorrhizin, and phlorizin) is obtained from apple 

 and pear trees, where it is most abundant at the tip of the shoots; it occurs in progres- 

 sively smaller quantities toward the base. The concentration is about twice as great in 

 the pear tree as in the apple tree. In the early summer, when the glucoside is present in 

 the greatest quantity, it may comprise 20% of the total solids, or 5 to 6% of the fresh 

 weight. 863 It has been widely used to produce a temporary glycosuria, largely for the 

 study of the intermediary metabolism. Lusk, 864 more than anyone else, is responsible 

 for standardizing and developing the quantitative basis for the use of phlorhizin in 

 metabolic experiments. When it is injected subcutaneously into a dog, in the amount 

 of 1 g. daily in oil, a complete diabetes obtains over a 24-hour period; thereafter the 

 glucosuria gradually wears off unless the dose is repeated. Deuel, Wilson, and Mil- 

 horat 865 adduced evidence that phlorhizin exerts its effect by primary action on the kid- 

 neys; the accompanying diabetic symptoms, such as ketosis, exaggerated glucose toler- 

 ance curves, and excretion of administered glucose, are secondary effects which can be 

 avoided if the primary action on the kidneys can be prevented. Nash 866 has written 

 a comprehensive review on phlorhizin diabetes. 



It was found that, when phlorhizin was given to rats, absorption Avas 

 practically zero over a six-hour period, irrespective of whether the fat was 



861 F. Verzar and L. Laszt, Biochem,. Z., 276, 1-10 (1935). 



862 J. von Mering, Deut. Gesell. inn. Med., Verhandl. 5ter Congr. inn. Med., Wies- 

 baden, 1886, 185-189; cited by L. V. Beck, J. Biol. Chem,, 143, 403-415 (1942), p. 403. 



863 E. M. Harvev, Oregon Agr. College, Exptl. Sta. Bull. No. 215, 5-23 (1925). 



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



866 H. J. Deuel, Jr., H. E. C. Wilson, and A. T. Milhorat, J. Biol. Chem., 7/,, 205-297 

 (1927). 



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



