Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1972 Jan;126(2):295–311. doi: 10.1042/bj1260295

The immediate effects of insulin and fructose on the metabolism of the perfused liver. Changes in lipoprotein secretion, fatty acid oxidation and esterification, lipogenesis and carbohydrate metabolism

D L Topping 1, P A Mayes 1
PMCID: PMC1178380  PMID: 5071176

Abstract

1. When livers from fed rats were perfused with blood containing elevated concentrations of rat insulin or blood to which fructose was added, the oxidation of free fatty acids was depressed and their esterification was increased. 2. Raised concentrations of insulin or addition of fructose increased secretion of triglyceride in very-low-density lipoproteins, but only insulin caused more of the free fatty acids taken up by the liver to be incorporated into very-low-density lipoproteins. 3. When insulin and fructose were added together the combined effect on oxidation and esterification of free fatty acids and on secretion of very-low-density lipoproteins was equal to the sum of the effects of either alone. No statistically significant interaction between the effects of fructose and insulin was found for any of the parameters investigated. 4. Bovine insulin had similar effects, in most respects, to comparable studies with raised concentrations of rat insulin. 5. Lipogenesis was increased in the livers treated with fructose plus bovine insulin. 6. A significant proportion of the fatty acids in very-low-density lipoproteins were derived either from the liver triglyceride pool or from lipogenesis. This fraction was increased both by treatment with insulin or fructose, and was augmented further when both insulin and fructose were present together. 7. The uptake of fructose by the perfused liver was similar to that found in vivo. It was unaffected by the presence of insulin. 8. Addition of fructose to the perfused liver caused perfusate lactate concentrations to increase, as a result of diminished hepatic uptake of lactate. 9. The uptake of free fatty acids by the perfused liver was unaffected by the addition of either insulin or fructose. 10. The distribution among the various lipid classes in plasma lipoproteins of label arising from the hepatic uptake of [14C]oleate was unaltered by the addition of either fructose or insulin. 11. It is suggested that the effects described are due principally to control of the balance between esterification of fatty acids and lipolysis of the ensuing triglyceride, fructose enhancing esterification and insulin inhibiting lipolysis.

Full text

PDF
295

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ALTMAN K. I., MILLER L. L., BLY C. G. The synergistic effect of cortisone and insulin on lipogenesis in the perfused rat liver as studied with alpha-C14-acetate. Arch Biochem Biophys. 1951 Apr;31(2):329–331. doi: 10.1016/0003-9861(51)90225-1. [DOI] [PubMed] [Google Scholar]
  2. BAKER N., SCHOTZ M. C. USE OF MULTICOMPARTMENTAL MODELS TO MEASURE RATES OF TRIGLYCERIDE METABOLISM IN RATS. J Lipid Res. 1964 Apr;5:188–197. [PubMed] [Google Scholar]
  3. BRADY R. O., GURIN S. The biosynthesis of radioactive fatty acids and cholesterol. J Biol Chem. 1950 Oct;186(2):461–469. [PubMed] [Google Scholar]
  4. BRADY R. O., LUKENS F. D. W., GURIN S. Hormonal influence upon the in vitro synthesis of radioactive fatty acids. Science. 1951 Apr 13;113(2937):413–415. doi: 10.1126/science.113.2937.413. [DOI] [PubMed] [Google Scholar]
  5. BRUCE H. M., PARKES A. S. Feeding and breeding of laboratory animals; a complete cubed diet for mice and rats. J Hyg (Lond) 1949 Jun;47(2):202–208. doi: 10.1017/s0022172400014479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bewsher P. D., Ashmore J. Ketogenic and lipolytic effects of glucagon on liver. Biochem Biophys Res Commun. 1966 Aug 12;24(3):431–436. doi: 10.1016/0006-291x(66)90178-1. [DOI] [PubMed] [Google Scholar]
  7. Butcher R. W., Sneyd J. G., Park C. R., Sutherland E. W., Jr Effect of insulin on adenosine 3',5'-monophosphate in the rat epididymal fat pad. J Biol Chem. 1966 Apr 10;241(7):1651–1653. [PubMed] [Google Scholar]
  8. CARLSON L. A. Determination of serum glycerides. Acta Soc Med Ups. 1959;64:208–213. [PubMed] [Google Scholar]
  9. Claycomb W. C., Bynagle J. K., Kilsheimer G. S. Hormone stimulation of ketogenesis in rat liver homogenates. Biochem Biophys Res Commun. 1969 Aug 7;36(3):414–419. doi: 10.1016/0006-291x(69)90580-4. [DOI] [PubMed] [Google Scholar]
  10. Farquhar J. W., Frank A., Gross R. C., Reaven G. M. Glucose, insulin, and triglyceride responses to high and low carbohydrate diets in man. J Clin Invest. 1966 Oct;45(10):1648–1656. doi: 10.1172/JCI105472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Felts J. M., Mayes P. A. A computer programme for the calculation of radioactivity data from liquid-scintillation counters fitted with external standards. Biochem J. 1967 Nov;105(2):735–739. doi: 10.1042/bj1050735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ford S., Jr, Bozian R. C., Knowles H. C., Jr Interactions of obesity, and glucose and insulin levels in hypertriglyceridemia. Am J Clin Nutr. 1968 Sep;21(9):904–910. doi: 10.1093/ajcn/21.9.904. [DOI] [PubMed] [Google Scholar]
  13. Guder W., Fröhlich J., Patzelt C., Wieland O. The effect of glucagon on the state of lysosomal enzymes in isolated perfused rat liver. FEBS Lett. 1970 Oct 16;10(4):215–218. doi: 10.1016/0014-5793(70)80631-7. [DOI] [PubMed] [Google Scholar]
  14. HAFT D. E., MILLER L. L. Alloxan diabetes and demonstrated direct action of insulin on metabolism of isolated perfused rat liver. Am J Physiol. 1958 Jan;192(1):33–42. doi: 10.1152/ajplegacy.1957.192.1.33. [DOI] [PubMed] [Google Scholar]
  15. Haft D. E. Studies of the metabolism of isolated livers of normal and alloxan-diabetic rats perfused with insulin. Diabetes. 1968 May;17(5):244–250. doi: 10.2337/diab.17.5.244. [DOI] [PubMed] [Google Scholar]
  16. Heimberg M., Weinstein I., Kohout M. The effects of glucagon, dibutyryl cyclic adenosine 3',5'-monophosphate, and concentration of free fatty acid on hepatic lipid metabolism. J Biol Chem. 1969 Oct 10;244(19):5131–5139. [PubMed] [Google Scholar]
  17. Heinz F., Junghänel J. Metabolitmuster in Rattenleber nach Fructoseapplikation. Hoppe Seylers Z Physiol Chem. 1969 Jul;350(7):859–866. [PubMed] [Google Scholar]
  18. Hepp K. D. Inhibition of glucagon-stimulated adenyl cyclase by insulin. FEBS Lett. 1971 Jan 30;12(5):263–266. doi: 10.1016/0014-5793(71)80193-x. [DOI] [PubMed] [Google Scholar]
  19. Howland R. J., Nowell N. W. The control of blood sugar in the laboratory rat and golden hamster. II. Investigations of plasma insulin concentrations. Acta Endocrinol (Copenh) 1969 Oct;62(2):283–288. doi: 10.1530/acta.0.0620283. [DOI] [PubMed] [Google Scholar]
  20. Jefferson L. S., Exton J. H., Butcher R. W., Sutherland E. W., Park C. R. Role of adenosine 3',5'-monophosphate in the effects of insulin and anti-insulin serum on liver metabolism. J Biol Chem. 1968 Mar 10;243(5):1031–1038. [PubMed] [Google Scholar]
  21. Jones A. L., Ruderman N. B., Herrera M. G. Electron microscopic and biochemical study of lipoprotein synthesis in the isolated perfused rat liver. J Lipid Res. 1967 Sep;8(5):429–446. [PubMed] [Google Scholar]
  22. KUO P. T., BASSETT D. R. DIETARY SUGAR IN THE PRODUCTION OF HYPERGLYCERIDEMIA. Ann Intern Med. 1965 Jun;62:1199–1212. doi: 10.7326/0003-4819-62-6-1199. [DOI] [PubMed] [Google Scholar]
  23. Kuo P. T., Feng L., Cohen N. N., Fitts W. T., Jr, Miller L. D. Dietary carbohydrates in hyperlipemia (hyperglyceridemia); hepatic and adipose tissue lipogenic activities. Am J Clin Nutr. 1967 Feb;20(2):116–125. doi: 10.1093/ajcn/20.2.116. [DOI] [PubMed] [Google Scholar]
  24. LEVINE R., FRITZ I. B. The relation of insulin to liver metabolism. Diabetes. 1956 May-Jun;5(3):209-19; discussion, 219-22. doi: 10.2337/diab.5.3.209. [DOI] [PubMed] [Google Scholar]
  25. MAHLER R., STAFFORD W. S., TARRANT M. E., ASHMORE J. THE EFFECT OF INSULIN ON LIPOLYSIS. Diabetes. 1964 May-Jun;13:297–302. [PubMed] [Google Scholar]
  26. MAYES P. A. Regulation of unesterified fatty acids of the plasma during the onset of starvation. Nature. 1962 Sep 15;195:1071–1072. doi: 10.1038/1951071a0. [DOI] [PubMed] [Google Scholar]
  27. MORTIMORE G. E., TIETZE F., STETTEN D., Jr Metabolism of insulin-I 131; studies in isolated, perfused rat liver and hindlimb preparations. Diabetes. 1959 Jul-Aug;8(4):307–314. doi: 10.2337/diab.8.4.307. [DOI] [PubMed] [Google Scholar]
  28. MUNTZ J. A., VANKO M. The metabolism of intraportally injected fructose in rat liver in vivo. J Biol Chem. 1962 Dec;237:3582–3587. [PubMed] [Google Scholar]
  29. Macdonald I. The effects of various dietary carbohydrates on the serum lipids during a five-day regimen. Clin Sci. 1965 Aug;29(1):193–197. [PubMed] [Google Scholar]
  30. Mayes P. A., Felts J. M. Determination of 14C-labelled ketone bodies by liquid-scintillation counting. Biochem J. 1967 Jan;102(1):230–235. doi: 10.1042/bj1020230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mayes P. A., Felts J. M. Regulation of fat metabolism of the liver. Nature. 1967 Aug 12;215(5102):716–718. doi: 10.1038/215716a0. [DOI] [PubMed] [Google Scholar]
  32. Menahan L. A., Wieland O. Interactions of glucagon and insulin on the metabolism of perfused livers from fasted rats. Eur J Biochem. 1969 May 1;9(1):55–62. doi: 10.1111/j.1432-1033.1969.tb00575.x. [DOI] [PubMed] [Google Scholar]
  33. Nikkilä E. A. Control of plasma and liver triglyceride kinetics by carbohydrate metabolism and insulin. Adv Lipid Res. 1969;7:63–134. doi: 10.1016/b978-0-12-024907-7.50009-9. [DOI] [PubMed] [Google Scholar]
  34. Ockner R. K., Hughes F. B., Isselbacher K. J. Very low density lipoproteins in intestinal lymph: origin, composition, and role in lipid transport in the fasting state. J Clin Invest. 1969 Nov;48(11):2079–2088. doi: 10.1172/JCI106174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ockner R. K., Hughes F. B., Isselbacher K. J. Very low density lipoproteins in intestinal lymph: role in triglyceride and cholesterol transport during fat absorption. J Clin Invest. 1969 Dec;48(12):2367–2373. doi: 10.1172/JCI106203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. PARK C. R., MORGAN H. E., HENDERSON M. J., REGEN D. M., CADENAS E., POST R. L. The regulation of glucose uptake in muscle as studied in the perfused rat heart. Recent Prog Horm Res. 1961;17:493–538. [PubMed] [Google Scholar]
  37. Pereira J. N., Jangaard N. O. Different rates of glucose and fructose metabolism in rat liver tissue in vitro. Metabolism. 1971 Apr;20(4):392–400. doi: 10.1016/0026-0495(71)90101-6. [DOI] [PubMed] [Google Scholar]
  38. RENOLD A. E., HASTINGS A. B., NESBETT F. B., ASHMORE J. Studies on carbohydrate metabolism in rat liver slices. IV. Biochemical sequence of events after insulin administration. J Biol Chem. 1955 Mar;213(1):135–146. [PubMed] [Google Scholar]
  39. Reaven G. M., Lerner R. L., Stern M. P., Farquhar J. W. Role of insulin in endogenous hypertriglyceridemia. J Clin Invest. 1967 Nov;46(11):1756–1767. doi: 10.1172/JCI105666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Richards K. C., Ruderman N. B., Herrera M. G. Effect of oleate concentration on its metabolism by the perfused rat liver. Biochim Biophys Acta. 1968 May 1;152(3):632–635. doi: 10.1016/0005-2760(68)90105-7. [DOI] [PubMed] [Google Scholar]
  41. STEIN Y., SHAPIRO B. Assimilation and dissimilation of fatty acids by the rat liver. Am J Physiol. 1959 Jun;196(6):1238–1241. doi: 10.1152/ajplegacy.1959.196.6.1238. [DOI] [PubMed] [Google Scholar]
  42. Senft G., Schultz G., Munske K., Hoffmann M. Influence of insulin on cyclic 3',5'-AMP phosphodiesterase activity in liver, skeletal muscle, adipose tissue, and kidney. Diabetologia. 1968 Dec;4(6):322–329. doi: 10.1007/BF01211766. [DOI] [PubMed] [Google Scholar]
  43. Sillero M. A., Sillero A., Sols A. Enzymes involved in fructose metabolism in lir and the glyceraldehyde metabolic crossroads. Eur J Biochem. 1969 Sep;10(2):345–350. doi: 10.1111/j.1432-1033.1969.tb00696.x. [DOI] [PubMed] [Google Scholar]
  44. TROUT D. L., ESTES E. H., Jr, FRIEDBERG S. J. Titration of free fatty acids of plasma: a study of current methods and a new modification. J Lipid Res. 1960 Apr;1:199–202. [PubMed] [Google Scholar]
  45. Tzagournis M., Chiles R., Ryan J. M., Skillman T. G. Interrelationships of hyperinsulinism and hypertriglyceridemia in young patients with coronary heart disease. Circulation. 1968 Dec;38(6):1156–1163. doi: 10.1161/01.cir.38.6.1156. [DOI] [PubMed] [Google Scholar]
  46. WEICHSELBAUM T. E., MARGRAF H. W., ELMAN R. Metabolism of intravenously infused fructose in man. Metabolism. 1953 Sep;2(5):434–449. [PubMed] [Google Scholar]
  47. Windmueller H. G., Spaeth A. E. De novo synthesis of fatty acid in perfused rat liver as a determinant of plasma lipoprotein production. Arch Biochem Biophys. 1967 Nov;122(2):362–369. doi: 10.1016/0003-9861(67)90206-8. [DOI] [PubMed] [Google Scholar]
  48. Woods H. F., Eggleston L. V., Krebs H. A. The cause of hepatic accumulation of fructose 1-phosphate on fructose loading. Biochem J. 1970 Sep;119(3):501–510. doi: 10.1042/bj1190501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Yudkin J., Kakkar V. V., Szanto S. Sugar intake, serum insulin and platelet adhesiveness in men with and without peripheral vascular disease. Postgrad Med J. 1969 Sep;45(527):608–611. doi: 10.1136/pgmj.45.527.608. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES