Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1984 Sep;74(3):1108–1111. doi: 10.1172/JCI111479

Time course and significance of changes in hepatic fructose-2,6-bisphosphate levels during refeeding of fasted rats.

M Kuwajima, C B Newgard, D W Foster, J D McGarry
PMCID: PMC425271  PMID: 6547962

Abstract

The time course of changes in hepatic fructose-2,6-bisphosphate (F-2,6-P2) and glycogen content was examined in fasted rats infused with glucose intragastrically or allowed to eat a chow diet ad lib. Initial values for the two parameters were approximately 0.4 nmol/g and 2 mg/g of tissue, respectively. Contrary to what might have been expected on the basis of reported studies with hepatocytes exposed to glucose (i.e., a rapid elevation of F-2,6-P2), the rise in F-2,6-P2 levels in vivo was a late event. It began only 4-5 h after glucose administration or refeeding, at which time glycogen content had reached approximately 35 mg/g of tissue. Thereafter, [F-2,6-P2] climbed rapidly, attaining fed values in the region of 10 nmol/g as glycogen stores became maximal (approximately 60 mg/g of tissue). Although the biochemical basis for these changes is still unclear, the delayed increase in [F-2,6-P2] is entirely consistent with the fact that much of the glycogen deposited in liver in the early postprandial phase is gluconeogenic in origin. The later rise in [F-2,6-P2] likely represents a key signal for the attenuation of gluconeogenic carbon flow into glycogen as the latter approaches repletion levels.

Full text

PDF
1108

Selected References

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

  1. Boyd M. E., Albright E. B., Foster D. W., McGarry J. D. In vitro reversal of the fasting state of liver metabolism in the rat. Reevaluation of the roles of insulin and glucose. J Clin Invest. 1981 Jul;68(1):142–152. doi: 10.1172/JCI110230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chaekal O. K., Boaz J. C., Sugano T., Harris R. A. Role of fructose 2,6-bisphosphate in the regulation of glycolysis and gluconeogenesis in chicken liver. Arch Biochem Biophys. 1983 Sep;225(2):771–778. doi: 10.1016/0003-9861(83)90088-7. [DOI] [PubMed] [Google Scholar]
  3. Chan T. M., Exton J. H. A rapid method for the determination of glycogen content and radioactivity in small quantities of tissue or isolated hepatocytes. Anal Biochem. 1976 Mar;71(1):96–105. doi: 10.1016/0003-2697(76)90014-2. [DOI] [PubMed] [Google Scholar]
  4. HERS H. G. The conversion of fructose-1-C14 and sorbitol-1-C14 to liver and muscle glycogen in the rat. J Biol Chem. 1955 May;214(1):373–381. [PubMed] [Google Scholar]
  5. Hers H. G., Hue L. Gluconeogenesis and related aspects of glycolysis. Annu Rev Biochem. 1983;52:617–653. doi: 10.1146/annurev.bi.52.070183.003153. [DOI] [PubMed] [Google Scholar]
  6. Hers H. G. The control of glycogen metabolism in the liver. Annu Rev Biochem. 1976;45:167–189. doi: 10.1146/annurev.bi.45.070176.001123. [DOI] [PubMed] [Google Scholar]
  7. Hers H. G., Van Schaftingen E. Fructose 2,6-bisphosphate 2 years after its discovery. Biochem J. 1982 Jul 15;206(1):1–12. doi: 10.1042/bj2060001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hostetler K. Y., Landau B. R. Estimation of the pentose cycle contribution to glucose metabolism in tissue in vivo. Biochemistry. 1967 Oct;6(10):2961–2964. doi: 10.1021/bi00862a001. [DOI] [PubMed] [Google Scholar]
  9. Hue L., Blackmore P. F., Shikama H., Robinson-Steiner A., Exton J. H. Regulation of fructose-2,6-bisphosphate content in rat hepatocytes, perfused hearts, and perfused hindlimbs. J Biol Chem. 1982 Apr 25;257(8):4308–4313. [PubMed] [Google Scholar]
  10. Hue L., van de Werve G., Jeanrenaud B. Fructose 2,6-bisphosphate in livers of genetically obese rats. Biochem J. 1983 Sep 15;214(3):1019–1022. doi: 10.1042/bj2141019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. LANGDON R. G., TAYLOR W. R. Intestinal absorption of glucose in the rat. Biochim Biophys Acta. 1956 Aug;21(2):384–385. doi: 10.1016/0006-3002(56)90027-0. [DOI] [PubMed] [Google Scholar]
  12. MARKS P. A., FEIGELSON P. Pathways of glycogen formation in liver and skeletal muscle in fed and fasted rats. J Clin Invest. 1957 Aug;36(8):1279–1284. doi: 10.1172/JCI103525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Neely P., El-Maghrabi M. R., Pilkis S. J., Claus T. H. Effect of diabetes, insulin, starvation, and refeeding on the level of rat hepatic fructose 2,6-bisphosphate. Diabetes. 1981 Dec;30(12):1062–1064. doi: 10.2337/diab.30.12.1062. [DOI] [PubMed] [Google Scholar]
  14. Newgard C. B., Foster D. W., McGarry J. D. Evidence for suppression of hepatic glucose-6-phosphatase with carbohydrate feeding. Diabetes. 1984 Feb;33(2):192–195. doi: 10.2337/diab.33.2.192. [DOI] [PubMed] [Google Scholar]
  15. Newgard C. B., Hirsch L. J., Foster D. W., McGarry J. D. Studies on the mechanism by which exogenous glucose is converted into liver glycogen in the rat. A direct or an indirect pathway? J Biol Chem. 1983 Jul 10;258(13):8046–8052. [PubMed] [Google Scholar]
  16. Newgard C. B., Moore S. V., Foster D. W., McGarry J. D. Efficient hepatic glycogen synthesis in refeeding rats requires continued carbon flow through the gluconeogenic pathway. J Biol Chem. 1984 Jun 10;259(11):6958–6963. [PubMed] [Google Scholar]
  17. Pilkis S. J., Chrisman T. D., El-Maghrabi M. R., Colosia A., Fox E., Pilkis J., Claus T. H. The action of insulin on hepatic fructose 2,6-bisphosphate metabolism. J Biol Chem. 1983 Feb 10;258(3):1495–1503. [PubMed] [Google Scholar]
  18. Pilkis S. J., El-Maghrabi M. R., Pilkis J., Claus T. H., Cumming D. A. Fructose 2,6-bisphosphate. A new activator of phosphofructokinase. J Biol Chem. 1981 Apr 10;256(7):3171–3174. [PubMed] [Google Scholar]
  19. Radziuk J. Sources of carbon in hepatic glycogen synthesis during absorption of an oral glucose load in humans. Fed Proc. 1982 Jan;41(1):110–116. [PubMed] [Google Scholar]
  20. Richards C. S., Uyeda K. Changes in the concentration of activation factor for phosphofructokinase in hepatocytes in response to glucose and glucagon. Biochem Biophys Res Commun. 1980 Dec 31;97(4):1535–1540. doi: 10.1016/s0006-291x(80)80040-4. [DOI] [PubMed] [Google Scholar]
  21. Riesenfeld G., Wals P. A., Golden S., Katz J. Glucose, amino acids, and lipogenesis in hepatocytes of Japanese quail. J Biol Chem. 1981 Oct 10;256(19):9973–9980. [PubMed] [Google Scholar]
  22. Sugden M. C., Watts D. I., Palmer T. N., Myles D. D. Direction of carbon flux in starvation and after refeeding: in vitro and in vivo effects of 3-mercaptopicolinate. Biochem Int. 1983 Sep;7(3):329–337. [PubMed] [Google Scholar]
  23. Uyeda K., Furuya E., Luby L. J. The effect of natural and synthetic D-fructose 2,6-bisphosphate on the regulatory kinetic properties of liver and muscle phosphofructokinases. J Biol Chem. 1981 Aug 25;256(16):8394–8399. [PubMed] [Google Scholar]
  24. Van Schaftingen E., Hers H. G. Inhibition of fructose-1,6-bisphosphatase by fructose 2,6-biphosphate. Proc Natl Acad Sci U S A. 1981 May;78(5):2861–2863. doi: 10.1073/pnas.78.5.2861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Van Schaftingen E., Hue L., Hers H. G. Control of the fructose-6-phosphate/fructose 1,6-bisphosphate cycle in isolated hepatocytes by glucose and glucagon. Role of a low-molecular-weight stimulator of phosphofructokinase. Biochem J. 1980 Dec 15;192(3):887–895. doi: 10.1042/bj1920887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Van Schaftingen E., Hue L., Hers H. G. Fructose 2,6-bisphosphate, the probably structure of the glucose- and glucagon-sensitive stimulator of phosphofructokinase. Biochem J. 1980 Dec 15;192(3):897–901. doi: 10.1042/bj1920897. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES