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. 1984 Feb 15;218(1):165–170. doi: 10.1042/bj2180165

Role of fructose 2,6-bisphosphate in the control by glucagon of gluconeogenesis from various precursors in isolated rat hepatocytes.

L Hue, R Bartrons
PMCID: PMC1153320  PMID: 6546872

Abstract

Hepatocytes from overnight-starved rats were incubated with 1-20 mM-fructose, -dihydroxyacetone, -glycerol, -alanine or -lactate and -pyruvate with or without 0.1 microM-glucagon. The production of glucose and lactate was measured, as was the content of fructose 2,6-bisphosphate. The concentrations of fructose (below 5 mM) and dihydroxyacetone (above 1 mM) that gave rise to an increase in fructose 2,6-bisphosphate were those at which a glucagon effect on the production of glucose and lactate could be observed. Glycerol had no effect on fructose 2,6-bisphosphate content or on production of lactate, and glucagon did not stimulate the production of glucose from this precursor. With alanine or lactate/pyruvate as substrates, glucagon stimulated glucose production whether the concentration of fructose 2,6-bisphosphate was increased or not. The extent of inactivation of pyruvate kinase by glucagon was not affected by the presence of the various gluconeogenic precursors. The role of fructose 2,6-bisphosphate in the effect of glucagon on gluconeogenesis from precursors entering the pathway at the level of triose phosphates or pyruvate is discussed.

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Selected References

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  1. Blair J. B., Cook D. E., Lardy H. A. Influence of glucagon on the metabolism of xylitol and dihydroxyacetone in the isolated perfused rat liver. J Biol Chem. 1973 May 25;248(10):3601–3607. [PubMed] [Google Scholar]
  2. Clark D. G., Filsell O. H., Topping D. L. Effects of fructose concentration on carbohydrate metabolism, heat production and substrate cycling in isolated rat hepatocytes. Biochem J. 1979 Dec 15;184(3):501–507. doi: 10.1042/bj1840501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Clark M. G., Kneer N. M., Bosch A. L., Lardy H. A. The fructose 1,6-diphosphatase-phosphofructokinase substrate cycle. A site of regulation of hepatic gluconeogenesis by glucagon. J Biol Chem. 1974 Sep 25;249(18):5695–5703. [PubMed] [Google Scholar]
  4. Claus T. H., Pilkis S. J., Park C. R. Stimulation by glucagon of the incorporation of U-14C-labeled substrates into glucose by isolated hepatocytes from fed rats. Biochim Biophys Acta. 1975 Sep 8;404(1):110–123. doi: 10.1016/0304-4165(75)90152-x. [DOI] [PubMed] [Google Scholar]
  5. Claus T. H., Schlumpf J. R., El-Maghrabi M. R., Pilkis S. J. Regulation of the phosphorylation and activity of 6-phosphofructo 1-kinase in isolated hepatocytes by alpha-glycerolphosphate and fructose 2,6-bisphosphate. J Biol Chem. 1982 Jul 10;257(13):7541–7548. [PubMed] [Google Scholar]
  6. Eggleston L. V., Woods H. F. Activation of liver pyruvate kinase by fructose-1-phosphate. FEBS Lett. 1970 Jan 15;6(1):43–45. doi: 10.1016/0014-5793(70)80038-2. [DOI] [PubMed] [Google Scholar]
  7. Engström L. The regulation of liver pyruvate kinase by phosphorylation--dephosphorylation. Curr Top Cell Regul. 1978;13:28–51. [PubMed] [Google Scholar]
  8. Exton J. H., Park C. R. Control of gluconeogenesis in liver. 3. Effects of L-lactate, pyruvate, fructose, glucagon, epinephrine, and adenosine 3',5'-monophosphate on gluconeogenic intermediates in the perfused rat liver. J Biol Chem. 1969 Mar 25;244(6):1424–1433. [PubMed] [Google Scholar]
  9. Feliú J. E., Hue L., Hers H. G. Hormonal control of pyruvate kinase activity and of gluconeogenesis in isolated hepatocytes. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2762–2766. doi: 10.1073/pnas.73.8.2762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Garrison J. C., Haynes R. C., Jr Hormonal control of glycogenolysis and gluconeogenesis in isolated rat liver cells. J Biol Chem. 1973 Aug 10;248(15):5333–5343. [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Hue L., Felíu J. E., Hers H. G. Control of gluconeogenesis and of enzymes of glycogen metabolism in isolated rat hepatocytes. A parallel study of the effect of phenylephrine and of glucagon. Biochem J. 1978 Dec 15;176(3):791–797. doi: 10.1042/bj1760791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hue L., Hers H. G. Utile and futile cycles in the liver. Biochem Biophys Res Commun. 1974 Jun 4;58(3):540–548. doi: 10.1016/s0006-291x(74)80454-7. [DOI] [PubMed] [Google Scholar]
  15. Hue L. The role of futile cycles in the regulation of carbohydrate metabolism in the liver. Adv Enzymol Relat Areas Mol Biol. 1981;52:247–331. doi: 10.1002/9780470122976.ch4. [DOI] [PubMed] [Google Scholar]
  16. Jarrett I. G., Clark D. G., Filsell O. H., Harvey J. W., Clark M. G. The application of microcalorimetry to the assessment of metabolic efficiency in isolated rat hepatocytes. Biochem J. 1979 Jun 15;180(3):631–638. doi: 10.1042/bj1800631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Katz J., Rognstad R. Futile cycles in the metabolism of glucose. Curr Top Cell Regul. 1976;10:237–289. doi: 10.1016/b978-0-12-152810-2.50013-9. [DOI] [PubMed] [Google Scholar]
  18. Katz J., Wals P. A., Golden S., Rognstad R. Recycling of glucose by rat hepatocytes. Eur J Biochem. 1975 Dec 1;60(1):91–101. doi: 10.1111/j.1432-1033.1975.tb20979.x. [DOI] [PubMed] [Google Scholar]
  19. Kitajima S., Uyeda K. A binding study of the interaction of beta-D-fructose 2,6-bisphosphate with phosphofructokinase and fructose-1,6-bisphosphatase. J Biol Chem. 1983 Jun 25;258(12):7352–7357. [PubMed] [Google Scholar]
  20. 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]
  21. Pilkis S. J., Riou J. P., Claus T. H. Hormonal control of [14C]glucose synthesis from [U-14C]dihydroxyacetone and glycerol in isolated rat hepatocytes. J Biol Chem. 1976 Dec 25;251(24):7841–7852. [PubMed] [Google Scholar]
  22. 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]
  23. Rognstad R. Effects of glucose and of lactate on phosphofructokinase flux during gluconeogenesis. Biochim Biophys Acta. 1981 Sep 4;676(3):373–378. doi: 10.1016/0304-4165(81)90173-2. [DOI] [PubMed] [Google Scholar]
  24. Rognstad R., Katz J. Effects of hormones and of ethanol on the fructose 6-P-fructose 1,6-P2 futile cycle during gluconeogenesis in the liver. Arch Biochem Biophys. 1976 Dec;177(2):337–345. doi: 10.1016/0003-9861(76)90447-1. [DOI] [PubMed] [Google Scholar]
  25. Ross B. D., Hems R., Krebs H. A. The rate of gluconeogenesis from various precursors in the perfused rat liver. Biochem J. 1967 Mar;102(3):942–951. doi: 10.1042/bj1020942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Van Schaftingen E., Lederer B., Bartrons R., Hers H. G. A kinetic study of pyrophosphate: fructose-6-phosphate phosphotransferase from potato tubers. Application to a microassay of fructose 2,6-bisphosphate. Eur J Biochem. 1982 Dec;129(1):191–195. doi: 10.1111/j.1432-1033.1982.tb07039.x. [DOI] [PubMed] [Google Scholar]
  28. Van den Berghe G. Metabolic effects of fructose in the liver. Curr Top Cell Regul. 1978;13:97–135. doi: 10.1016/b978-0-12-152813-3.50008-2. [DOI] [PubMed] [Google Scholar]
  29. Veneziale C. M. Gluconeogenesis from D-glyceraldehyde and dihydroxyacetone in isolated rat liver. Stimulation by glucagon. Biochemistry. 1972 Aug 15;11(17):3286–3289. doi: 10.1021/bi00767a025. [DOI] [PubMed] [Google Scholar]
  30. Veneziale C. M. Gluconeogenesis from fructose in isolated rat liver. Stimulation by glucagon. Biochemistry. 1971 Aug 31;10(18):3443–3447. doi: 10.1021/bi00794a020. [DOI] [PubMed] [Google Scholar]

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