Abstract THE APPEARANCE of fatty degeneration in the livers of depancreatized dogs is evidence of a metabolic defect presumably related to the metabolism and utilization of fats. The utilization of fats for energy begins with phosphorylation and transformation to phospholipids.1 Therefore, it seemed reasonable to ascertain the rate of phospholipid formation in depancreatized dogs maintained on insulin in order to clarify the nature of their metabolic defect. The content of a recently injected isotope in a large organic complex, expressed as a function of time, constitutes a measure of the rate of synthesis of the large organic complex. In this paper a study of phospholipid formation is described in which the incorporation of radioactive phosphorus into the molecule is used as an indicator of the rate of formation of the phospholipid. Our findings suggest that in the absence of the pancreas in the dog phosphorylation of fat is unable to References 1. Deuel, H. J.; Murray, S.; Hallman, L. F., and Tyler, D. B.: Studies on Ketosis: XII. The Effect of Choline on the Ketonuria of Fasting Rats Following a High Fat Diet , J. Biol. Chem. 120:277-288, 1937. 2. Best, C. H., and Hershey, J. M.: Further Observations on the Effects of Some Component of Crude Lecithine on Depancreatized Animals , J. Physiol. 75:49-55, 1932. 3. Fisher, N. F.: Attempts to Maintain the Life of Totally Pancreatectomized Dogs Indefinitely by Insulin , Am. J. Physiol. 67:634-643, 1924. 4. Chaikoff, I. L.; Entenman, C., and Montgomery, M. L.: The Mechanism of Action of the Antifatty Liver Factor of the Pancreas: I. Its Relationship to Plasma Choline , J. Biol. Chem. 160:387-395, 1945. 5. Clark. D. E.; Eilert, M. L., and Dragstedt, L. R.: The Lipotropic Action of Lipocaic , Am. J. Physiol. 148:620-625, 1943. 6. Dragstedt, L. R.; Van Prohaska, J., and Harms, H. P.: Observations on a Substance in Pancreas (a Fat-Metabolizing Hormone) Which Permits Survival and Prevents Liver Changes in Pancreatectomized Dogs , Am. J. Physiol. 117:175-181, 1936. 7. Entenman, C.; Chaikoff, I. L., and Montgomery, M. L.: The Preparation of Fractions from Pancreas That Prevent Fatty Livers in Depancreatized Dogs Maintained with Insulin , J. Biol. Chem. 155:573-578, 1944. 8. Van Prohaska, J.; Dragstedt, L. R., and Harms, H. P.: The Relation of Pancreatic Juice to the Fatty Infiltration and Degeneration of the Liver in Depancreatized Dogs , Am. J. Physiol. 117:166-174, 1936. 9. Chaikoff, I. L.; Entenman, C., and Montgomery. M. L.: The Mechanism of Action of the Antifatty Liver Factor of the Pancreas: III. A Comparison of Hydrolyzed and Unhydrolyzed Casein in the Prevention of Fatty Livers in the Completely Depancreatized Dog Maintained with Insulin , J. Biol. Chem. 168:177-181, 1947. 10. Chaikoff, I. L., and Entenman, C.: Antifatty Liver Factor of the Pancreas—Present Status , Advances Enzymol. 8:171-202, 1948. 11. Thorn, G. W.; Bayles, T. B.; Massell, B. F.; Forsham, P. H.; Hill, S. R., Jr., and Warren, J. B.: Studies on the Relation of Pituitary-Adrenal Function to Rheumatic Disease , New England J. Med. 241:529-537, 1949.Crossref 12. Dragstedt, L. R.; Allen, J. G.; Julian, O. C., and Stinger, D.: Lipocaic and Ketonemia in Pancreatic Diabetes , Am. J. Physiol. 135:133-136, 1941. 13. Best, C. H.; Ferguson, G. C., and Hershey, J. M.: Choline and Liver Fat in Diabetic Dogs , J. Physiol 79:94-102, 1933 14. Thorogood, E., and Zimmermann, B.: The Effects of Pancreatectomy on Glycosuria and Ketosis in Dogs Made Diabetic with Alloxan , Endocrinology 37:191-200, 1945.Crossref 15. Entenman, C.; Chaikoff, I. L., and Zilversmit, D. B.: The Removal of Plasma Phospholipides as a Function of the Liver: The Effect of Exclusion of the Liver on the Turnover Rate of Plasma Phospholipides as Measured with Radioactive Phosphorus , J. Biol. Chem. 166:15-23, 1946. 16. (a) Chaikoff, I. L.; Zilversmit, D. B., and Entenman, C.: Phospholipid Metabolism in Diabetes: Turnover Rate of Plasma Phospholipids in Completely Depancreatized Dogs , Proc. Soc. Exper. Biol. & Med. 68:6-9, 1948. 17. (b) Friedlander, H. D.; Chaikoff, I. L., and Entenman, C.: The Effect of Ingested Choline on the Turnover of Plasma Phospholipids , J. Biol. Chem. 158:231-238, 1945. 18. (c) Perlman, I., and Chaikoff, I. L.: Radioactive Phosphorus as an Indicator of Phospholipid Metabolism: V. On the Mechanism of Action of Choline upon the Liver of the Fat-Fed Rat , J. Biol. Chem. 127:211-220, 1939. 19. (d) Zilversmit, D.; Entenman, C.; Fishler, M. C., and Chaikoff, I. L.: The Turnover Rate of Phospholipids in the Plasma of the Dog as Measured with Radioactive Phosphorus , J. Gen. Physiol. 26:333-340, 1943. 20. Cowgill, G. R.: An Improved Procedure for Metabolism Experiments , J. Biol. Chem. 56:725-737, 1923. 21. Supplied by Mead-Johnson & Company. 22. The Biophysical Laboratories of the Harvard Medical School, under Dr. A. K. Solomon, processed the radiophosphorus. 23. Fiske, C. H., and Subbarow, Y.: The Colorimetric Determination of Phosphorus , J. Biol. Chem. 66:375-400, 1925. 24. T=[unk]1−[unk]2/(σ1)2/n1+(σ2)2/n2 ([unk]1 and [unk]2 represent the respective means, where n1 and n2 represent the numbers of each series, and σ=Σ d2/n−1 A ratio of 2.5 or higher indicates that the difference between the means is 2.5 or more times the probable error of the difference. 25. Dragstedt, L. R.: The Role of the Pancreas in Arteriosclerosis , Biol. Symposia 11:118-132, 1945.
A.M.A. Archives Surgery – American Medical Association
Published: Dec 1, 1950