PHOSPHORUS CHANGES DURING THE ABSORPTION OF OIL AND GLUCOSE

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1 PHOSPHORUS CHANGES DURING THE ABSORPTION OF OIL AND GLUCOSE BY RAYMOND REISER* (If rwm the Department 0~ Medicine, Duke University School of Medicine, Durham, North Carolina, and the Department of Animal Husbandry, North Carolina State College, Raleigh) (Received for publication, April 15, 1940) These experiments on the relationship of phosphorus to the metabolism of fat and glucose were part of a general plan to test the hypot,hexis proposed by Verzar (1) that the major symptoms of sprue, the faulty absorption of fats and carbohydrates, may bc due to a breakdown in the phosphorylating mechanism. With the exceptions of the changes in the blood serum and muscles after glucose ingestion the normal relationships of the phosphorus changes in the body to the ingestion of fat and glucose have been very little studied. The present work is a report of these normal changes. The first phase of the work was a study of the changes in serum and urinary inorganic phosphate in humans after the ingestion of olive oil and glucose. The second phase was an investigation of the phosphate changes in the duodenal mucosa, liver, and kidney of swine during the absorption of cottonseed oil and glucose. Procedure and Methods Thrt strum and urinary phosphate studies were conducted on humans. The subjects were either laborat,ory workers or patient,s at Duke Hospital who had recovered from minor ailments or accidents and were about to be discharged. Except when stated otherwise, the subjects remained in bed during the entire course of the experiment and for at least 15 hours before. At 7.00 a.m., 13 hours after the last meal, urine * Anna H. Ilancs Research Fellow in Medicine, Duke University,

2 304 P Metabolism during Absorption was voided and the subject received a glass of water. Just before 8.00 a.m. urine was voided again and immediately afterward the test meal and a glass of water were given. Blood and urine samples were taken, and a glass of water was given at 8.30, 9.00, 10.00, a.m., and in the experiments with oil at noon. The test meal was either 50 gm. of glucose in a glass of water with the juice of half a lemon or 50 gm. of olive oil. Three subjects were given an intravenous glucose t>olerance test, also. 25 gm. of glucose were injected as a 50 per cent solution and the serum phosphorus determined a, 4, 1, 2, and 3 hours afterwards. The urinary phosphorus was determined at the same times and intervals as it was for the test after oral administration of glucose. The swine used in the studies were pure bred Duroc-Jerseys that had been on experiment t,o determine the relative values of different protein supplements in their nutrition. They had all been on the same diet for several weeks before these experiments. They were about 7 months old and weighed approximately 225 pounds. Three groups of five animals each were used. One group was slaughtered in the fasting state. One group was fed 200 gm. of glucose 1 hour and the other 200 gm. of cottonseed oil 2 hours before being slaughtered. The animals were held on their backs and the oil or glucose, the latter as a 50 per cent solution, poured into their mouths. They swallowed readily. The swine were killed by exsanguination and the tissues frozen with solid carbon dioxide as soon as possible. 5 gm. samples of frozen tissues were weighed to the nearest decigram, ground in a mortar with 10 per cent trichloroacetic acid without sand, and transferred to 50 cc. volumetric flasks by means of dropping pipettes. They were allowed to stand a few hours with occasional shaking, filtered, and placed in t,he ice box overnight. The determinations were made the next day. 5 gm. were weighed for moisture det,ermination. All phosphorus analyses were made according to the Fiske and Subbarow procedure (2) except that the perchloric acid digestion described by King (3) was used for the total phosphorus determination. The difference between the t,otal acid-soluble phosphorus and the inorga,nic phosphorus will be referred to as ester phosphorus.

3 R. Reiser 305 DISCUSSION In four experiments on three individuals the phosphorus excretion in the fasting state was shown to be at a minimum between 9 and I1 a.m. This is in agreement with the values given in the literature (4). Table I shows the effect of the ingestion of 50 gm. of olive oil on the rate of phosphorus excretion in the urine. All nine experiments show a pronounced decrease in phosphorus excretion, the maximum decrease occurring 1 hour after the ingestion of the oil. This decrease is independent of the diurnal change, being much TABLE h fect of Ingestion of 50 Gm. of Olive Oil upon Serum Inorganic Phosphorus and Rate of Phosphorus Excretion in Man HrsAisjfter Time a.n. Fasting SMll- 3le experimerit cbknpt Serum phosphorus Extremes per cent change to f I P 67 cent mg., :hange per hr I Rate of excretion Extremes per cent change MfX%n -84 to f I18 - $42 greater and occurring earlier. Youngburg (5) determim :C 1 the urinary phosphorus excretion after normal breakfasts and after similar breakfasts to which olive oil had been added. On the basis of the total excretion for 7 hours after the meal he concluded that there was an increase rather than a decrease in the amount of phosphorus excreted. However, he recorded the excretion at hourly intervals and his data show that in three of his four experiments the phosphorus excreted in the 1st hour was reduced by more than twice as much after the fat meal as after the normal meal. The effects of the ingestion of olive oil on the serum inorganic phosphate are also recorded in Table I. In seven of the eight

4 Time -- a.?n TABLE II Effect of Glucose Administration upon Rate of Phosphorus Excretion in Man 1 de experimerit mg. oer hr In bed EXtiEZXlGS per cent change +100 to -55 f $ L -75 Ingestion of 50 gm. glucose -Iper cent mg. change per hr I / 11 Sample experiments QZL Walking Extremes per cent change +67 to I Q E Mean e* ten.hange I -I- 1 Sam- de experimerit Injection of 25 gm. glucose In bed Extremes pamghr.. I per cent change to fl Jel cent change I - I

5 R. Reiser 307 experiment>s performed there was a significant drop in this value $ hour and in all the experiment,s 1 hour after the ingestion of t,hc oil. In a fasting, resting person the serum inorganic phosphorus remains constant in the morning (6, 7). Table II shows the changes in urinary phosphorus excretion after oral and intravenous administration of glucose. The six subjects who remained in bed were awake but at completc rest, during the entire course of the experiment. They had been in bed from 13 to 15 hours before the experiments began. Four experiments were performed on three persons who were standing and walking about the laboratory during the course of the experiments. The three subjects who received the intravenous injections of glucose remained in bed. In all thirteen of the experiments there was an increase in the phosphorus excretion during the second half hour after the glucose administration. It was slight in a few cases but very marked in all the others. This increase has an added significance when it is recalled t>hat in the fasting state there is a pronounced decrease in urinary phosphorus excretion at the same hour (4). This increase in phosphorus excretion after glucose administration is contrary to t,he commonly accepted belief. A study of the literature, however, shows that> there is no unanimity of opinion on this subject. Katayama (8) and Wolbergs (9) report increased excretion of phosphate after glucose ingestion in man. Blatherwick, Bell, and Hill (10) in five experiments out of ten showed an increase in phosphorus excretion aft,er glucose ingestion by human subjects. The data of Sokhey and Allen (I 1) which are often quoted as showing a decrease in urinary phosphate after administration of glucose by stomach tube to dogs actually show an increase in two out of three normal animals during the first 3 hour period. Bachmann, Haldi, and Ensor (12) could find no change in the urinary phosphorus excretion after the ingestion of glucose by humans. On the other hand, Perlzweig, Latham, and Keefer (13), Barrenscheen and coworkers (14), and Wierzuchowski and coworkers (15) found a decrease in phosphorus excretion after glucose ingestion. Fiske (16) found a decrease in urinary phosphorus after sucrose ingestion. Harrop and Benedict (17), Sokhey and Allen*( II), Blatherwick and coworkers (lo), Wigglesworth, Woodrow, Smith, and Winter

6 308 P Metabolism during Absorption (18)) Gortz (19), and many others have shown conclusively that the administration of insulin does lower phosphorus excretion in the urine. It does not follow, however, that the administration of insulin and sugar should have the same effect upon urinary phosphorus. Insulin produces a hypoglycemia and glucose a hyperglycemia. Iversen and Jacobsen (20) have shown that with a rising glycemia there is an increased elimination of phosphorus and that a lowering of blood sugar causes a decrease in phosphorus excretion. In all of these experiments there was a decrease in serum inorganic phosphate after either the oral or intravenous administra- Fasting TABLE Phosphorus Content of Swine Organs during Absorplion The values are given in mg. per cent after glucose 2 1x3. after oil III 1~0~anic P E k&i- Maximum Minimum Mean Maximum Minimum Mean Maximum Minimum Mean F Liver Inortnio P,E kter F Kidney Inoranic P,E lion of glucose. This is in complete agreement with the literature (21) and Dhe accepted belief. Analysts of swine organs after oil ingestion were made in an effort to find in which organs the phosphorus is mobilized. A few attempts to catheterize sows after food ingestion were made but it was decided that the struggles of the animals would have a greater effect on the values than the food. A study of Table III shows that after oil ingestion there is a marked increase in the phosphorus of the duodenal mucosa, liver, and kidney. These increases are mainly in the ester fraction, an increase in the inorganic fraction being significant in the mucosa :ster P

7 R. Reiser only. The function of these increases is conjectural. Borri (22) has also reported an increase in soluble phorphorus of the intestinal mucosa during oil absorption and attributed it to a breakdown in lecithalbumin to supply glycerol for the resynthesis of triglycerides. Laszt and Sullmann (23) obtained conflicting results in testing for an increase in acid-soluble phosphorus in the intestinal mucosa of rats absorbing olive oil. Since the liver is said to play an important r&e in the intermediary metabolism of fat, and the phosphorylation of the fat is a possible stage in that metabolism, the increase in liver phosphate during fat absorption is a logical finding. The explanation for the increase in kidney phosphate is not so apparent. In Table III are also presented the phosphate changes in swine organs after t,he ingestion of glucose. The decrease in the inorganic fraction and increase in the ester fraction in the intestinal mucosa are similar to the results recorded by Laszt and Sullmann (23) except that these authors found no increase in total acidsoluble phosphorus, the increase in the ester fraction being equal to the decrease in the inorganic fraction. There is no significant change in phosphate fractions of the liver. Cori and Goltz (24) found an increase in inorganic phosphorus in the liver after insulin injection but no evidence of increased hexosc phosphate formation. As pointed out above, it should not be assumed that the injection of insulin and the administration of glucose have the same effect on the mobilization of phosphates. Fenn (25) found a decrease in the inorganic and an increase in the ester phosphates of the liver during the active assimilation of starch and sucrose, while Takahisa (26) found an increase in t)hc inorganic phosphate of rabbit livers after the oral administration of glucose. There is no change in the inorganic phosphate of the kidney during glucose absorption but there is a possible increase in the ester fraction. The function of this additional phosphate may be the increased resorption of glucose from the kidney tubules due to the alimentary hyperglycemia. There was an increase in dry substance in the intestinal mucosa during absorption. This was especially significant after glucose ingestion and might be due to simple osmosis a~ a result, of the high concentration of the sugar in the intestinc. The mean per-

8 310 P Metabolism during Absorption centage of dry substance in the mucosa was as follows: during fasting 15.9, after oil 17.8, after glucose SUMMARY 1. There is a decrease in serum and urinary inorganic phosphate after the ingestion of olive oil by humans. 2. There is a decrease in serum but an increase in urinary phosphorus after the oral or intravenous administ,ration of glucose to humans. 3. During the absorption of glucose by swine there is (a) a decrease in the inorganic and an increase in the ester phosphorus of the duodenal mucosa, (b) no significant change in the phosphate fractions of the liver, and (c) no change in the inorganic but an increase in the ester phosphate of the kidney. 4. During the absorption of cot,tonseed oil by swine there is (a) an increase in both phosphate fractions of the duodenal mucosa, (b) no change in the inorganic but an increase in the est,er phosphate of the liver, and (c) no change in inorganic but an increase in ester phosphate of the kidney. 5. There is an increase in dry substance in the duodenal mucosa of swine during the absorption of glucose. The author is happy to acknowledge the helpful cooperation of Dr. Frederic M. Hanes of the Department of Medicine of Duke University and of Professor Earl H. Hostetler and Mr. Dalton Swaff ar of the Department of Animal Husbandry, Xorth Carolina State College. BIBLIOGRAPHY 1. VcrsBr, F., Am. J. Digest. Dis. and Nutrition, 4, 545 (1937). 2. Fiske, C. I-i., and Subbarow, Y., J. Iliol. Chem., 66, 375 (1925). 3. King, E. J., Biochem. J., 26, 292 (1932). 4. Fiske, C. H., J. Biol. Chem., 49, 171 (1921). 5. Youngburg, G. E., J. Lab. und Clin. Med., 20, 1929 (1937). 6. Havard, R. E., and Reay, G. A., Biochem. J., 19, 882 (1925). 7. Farquharson, 12. F., and Tibbetts, D. M., J. Clin. Inv., 10, 271 (1931). 8. Katayama, I., J. Lab. and Clin. Med., 11, 1024 (1926). 9. Wolbergs, H., Z. physiol. Chem., 238, 23 (1936). 10. Blatherwick, IT. R., Bell, M., and Hill, E., J. Biol. Chem., 61,241 (1924). Il. Sokhey, S. S., and Allen, F. V., Biochem. J., 18, 1170 (1924). 12. Bschmnnn, G., Haldi, J., and Ensor, C., Am. J. Physiol., 124,77 (1938).

9 R. Reiser 13. Perlaweig, W. A., Latham, E., and Keefer, S. C., Proc. Sot. Exp. Biol. and Med., 21, 33 (1933). 14. Barrenscheen, H. K., Doleschall, F., and Popper, L., Biochem. Z., 177, 50 (1926). 15. Wierzuchowski, M., Pieskaw, W., and Owsiany, E., Biochem. Z., 230, 146 (1931). 16. Fiske, C. H., Proc. Am. Sot. Biol. Chem., J. Biol. Chem., 41, p. lix (1920). 17. Harrop, G. A., Jr., and Benedict, E. M., J. Biol. Chem., 69, 683 (1924). 18. Wigglesworth, V. B., Woodrow, C. E., Smith, W., and Winter, I,. B., J. Physiol., 67, 447 (1923). 19. Gortz, S., J. Am. Med. Assn., 96, 382 (1930). 20. Iversen, P., and Jacobsen, E., Skand. Arch. Physiol., 71, 260 (1935). 21. Bolliger, A., and Hartman, F. W., J. Biol. Chem., 64, 91 (1925). Hartman, F. W., and Foster, D. P., Am. J. Clin. Path., 2, 289 (1926). 22. Borri, A., Arch. Verdauungskr., 12, 301 (1906). 23. Laszt, L., and Sullmann, H., Biochem. Z., 278, 401 (1935). 24. Cori, C. F., and Goltz, H. L., Am. J. Physiol., 72, 256 (1925). 25. Fenn, W. O., J. Biol. Chem., 128, 297 (1939). 26. Takahisa, T., Proc. Japan. Pharmacol. Sot., Japan. J. Med. SC., Pharmacol., 8, 117 (1934); Chem. Abst., 29, 2236 (1935).

10 PHOSPHORUS CHANGES DURING THE ABSORPTION OF OIL AND GLUCOSE Raymond Reiser J. Biol. Chem. 1940, 135: Access the most updated version of this article at Alerts: When this article is cited When a correction for this article is posted Click here to choose from all of JBC's alerts This article cites 0 references, 0 of which can be accessed free at tml#ref-list-1