Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1978 Dec 15;176(3):791–797. doi: 10.1042/bj1760791

Control of gluconeogenesis and of enzymes of glycogen metabolism in isolated rat hepatocytes. A parallel study of the effect of phenylephrine and of glucagon

Louis Hue 1, Juan Emilio Felíu 1,*, Henri-Géry Hers 1
PMCID: PMC1186302  PMID: 747652

Abstract

Hepatocytes isolated from the livers of fed rats were used for a comparative study of the effects of phenylephrine, vasopressin and glucagon on gluconeogenesis and on enzymes of glycogen metabolism. When hepatocytes were incubated in the presence of Ca2+, phenylephrine stimulated gluconeogenesis from pyruvate less than did glucagon, but, in contrast with this hormone, it did not affect the activities of protein kinase and pyruvate kinase, nor the concentration of phosphoenolpyruvate, and it did not decrease the release of 3H2O from [6-3H]glucose. The effects of vasopressin were similar to those of phenylephrine. Gluconeogenesis from fructose was also stimulated by phenylephrine and, more markedly, by glucagon at the expense of the conversion of fructose into lactate. Insulin was able to antagonize the stimulatory effect of phenylephrine on gluconeogenesis from pyruvate. When Ca2+ was removed from the incubation medium, phenylephrine still stimulated gluconeogenesis from pyruvate, but it also caused an activation of protein kinase and an inactivation of pyruvate kinase; accordingly, the concentration of phosphoenolpyruvate was increased, and, in contrast, vasopressin had no effect on all these parameters. The property of phenylephrine to cause the activation of glycogen phosphorylase was decreased by glucose or by the absence of Ca2+; it was abolished when these two conditions were combined. Glycogen synthase was inactivated by phenylephrine in the presence or the absence of Ca2+, although presumably by different mechanisms.

Full text

PDF
791

Selected References

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

  1. Assimacopoulos-Jeannet F. D., Blackmore P. F., Exton J. H. Studies on alpha-adrenergic activation of hepatic glucose output. Studies on role of calcium in alpha-adrenergic activation of phosphorylase. J Biol Chem. 1977 Apr 25;252(8):2662–2669. [PubMed] [Google Scholar]
  2. Blair J. B., Cimbala M. A., Foster J. L., Morgan R. A. Hepatic pyruvate kinase. Regulation by glucagon, cyclic adenosine 3'-5'-monophosphate, and insulin in the perfused rat liver. J Biol Chem. 1976 Jun 25;251(12):3756–3762. [PubMed] [Google Scholar]
  3. Bontemps F., Hue L., Hers H. G. Phosphorylation of glucose in isolated rat hepatocytes. Sigmoidal kinetics explained by the activity of glucokinase alone. Biochem J. 1978 Aug 15;174(2):603–611. doi: 10.1042/bj1740603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chan T. M., Exton J. H. alpha-Adrenergic-mediated accumulation of adenosine 3':5' monophosphate in calcium-depleted hepatocytes. J Biol Chem. 1977 Dec 10;252(23):8645–8651. [PubMed] [Google Scholar]
  5. Cherrington A. D., Assimacopoulos F. D., Harper S. C., Corbin J. D., Park C. R., Exton J. H. Studies on the alpha-andrenergic activation of hepatic glucose output. II. Investigation of the roles of adenosine 3':5'-monophosphate and adenosine 3':5'-monophosphate-dependent protein kinase in the actions of phenylephrine in isolated hepatocytes. J Biol Chem. 1976 Sep 10;251(17):5209–5218. [PubMed] [Google Scholar]
  6. Exton J. H., Harper S. C. Role of cyclic AMP in the actions of catecholamines on hepatic carbohydrate metabolism. Adv Cyclic Nucleotide Res. 1975;5:519–532. [PubMed] [Google Scholar]
  7. 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]
  8. Felíu J. E., Hue L., Hers H. G. Regulation in vitro and in vivo of adenosine 3':5'-monophosphate-dependent inactivation of rat-liver pyruvate kinase type L. Eur J Biochem. 1977 Dec;81(3):609–617. doi: 10.1111/j.1432-1033.1977.tb11988.x. [DOI] [PubMed] [Google Scholar]
  9. Hems D. A. Short-term hormonal control of hepatic carbohydrate and lipid catabolism. FEBS Lett. 1977 Aug 15;80(2):237–245. doi: 10.1016/0014-5793(77)80449-3. [DOI] [PubMed] [Google Scholar]
  10. Hems D. A., Whitton P. D. Stimulation by vasopressin of glycogen breakdown and gluconeogenesis in the perfused rat liver. Biochem J. 1973 Nov;136(3):705–709. doi: 10.1042/bj1360705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Hue L., Bontemps F., Hers H. The effects of glucose and of potassium ions on the interconversion of the two forms of glycogen phosphorylase and of glycogen synthetase in isolated rat liver preparations. Biochem J. 1975 Oct;152(1):105–114. doi: 10.1042/bj1520105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hue L., Felíu J. E. Hormonal regulation of glycogenolysis and gluconeogenesis in isolated rat hepatocytes. Biochem Soc Trans. 1978;6(1):29–33. doi: 10.1042/bst0060029. [DOI] [PubMed] [Google Scholar]
  14. Hutson N. J., Brumley F. T., Assimacopoulos F. D., Harper S. C., Exton J. H. Studies on the alpha-adrenergic activation of hepatic glucose output. I. Studies on the alpha-adrenergic activation of phosphorylase and gluconeogenesis and inactivation of glycogen synthase in isolated rat liver parenchymal cells. J Biol Chem. 1976 Sep 10;251(17):5200–5208. [PubMed] [Google Scholar]
  15. 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]
  16. Keppens S., Vandenheede J. R., De Wulf H. On the role of calcium as second messenger in liver for the hormonally induced activation of glycogen phosphorylase. Biochim Biophys Acta. 1977 Feb 28;496(2):448–457. doi: 10.1016/0304-4165(77)90327-0. [DOI] [PubMed] [Google Scholar]
  17. Keppens S., de Wulf H. The activation of liver glycogen phosphorylase by vasopressin. FEBS Lett. 1975 Mar 1;51(1):29–32. doi: 10.1016/0014-5793(75)80848-9. [DOI] [PubMed] [Google Scholar]
  18. Kirk C. J., Hems D. A. Hepatic action of vasopressin: lack of a role for adenosine-3',5'-cyclic monophosphate. FEBS Lett. 1974 Oct 1;47(1):128–131. doi: 10.1016/0014-5793(74)80441-2. [DOI] [PubMed] [Google Scholar]
  19. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  20. PATTERSON M. S., GREENE R. C. MEASUREMENT OF LOW ENERGY BETA-EMITTERS IN AQUEOUS SOLUTION BY LIQUID SCINTILLATION COUNTING OF EMULSIONS. Anal Chem. 1965 Jun;37:854–857. doi: 10.1021/ac60226a017. [DOI] [PubMed] [Google Scholar]
  21. Pilkis S. J., Claus T. H., Johnson R. A., Park C. R. Hormonal control of cyclic 3':5'-AMP levels and gluconeogenesis in isolated hepatocytes from fed rats. J Biol Chem. 1975 Aug 25;250(16):6328–6336. [PubMed] [Google Scholar]
  22. Riou J. P., Claus T. H., Pilkis S. J. Control of pyruvate kinase activity by glucagon in isolated hepatocytes. Biochem Biophys Res Commun. 1976 Dec 6;73(3):591–599. doi: 10.1016/0006-291x(76)90851-2. [DOI] [PubMed] [Google Scholar]
  23. Rognstad R., Katz J. Role of pyruvate kinase in the regulation of gluconeogenesis from L-lactate. J Biol Chem. 1977 Mar 25;252(6):1831–1833. [PubMed] [Google Scholar]
  24. Sherline P., Lynch A., Glinsmann W. H. Cyclic AMP and adrenergic receptor control of rat liver glycogen metabolism. Endocrinology. 1972 Sep;91(3):680–690. doi: 10.1210/endo-91-3-680. [DOI] [PubMed] [Google Scholar]
  25. Stalmans W. The role of the liver in the homeostasis of blood glucose. Curr Top Cell Regul. 1976;11:51–97. doi: 10.1016/b978-0-12-152811-9.50009-2. [DOI] [PubMed] [Google Scholar]
  26. Stubbs M., Kirk C. J., Hems D. A. Role of extracellular calcium in the action of vasopressin on hepatic glycogenolysis. FEBS Lett. 1976 Oct 15;69(1):199–202. doi: 10.1016/0014-5793(76)80686-2. [DOI] [PubMed] [Google Scholar]
  27. Tolbert M. E., Butcher F. R., Fain J. N. Lack of correlation between catecholamine effects on cyclic adenosine 3':5'-monophosphate and gluconeogenesis in isolated rat liver cells. J Biol Chem. 1973 Aug 25;248(16):5686–5692. [PubMed] [Google Scholar]
  28. Walsh D. A., Ashby C. D., Gonzalez C., Calkins D., Fischer E. H. Krebs EG: Purification and characterization of a protein inhibitor of adenosine 3',5'-monophosphate-dependent protein kinases. J Biol Chem. 1971 Apr 10;246(7):1977–1985. [PubMed] [Google Scholar]
  29. van Berkel T. J., Kruijt J. K., Koster J. F., Hülsmann W. C. Cyclic nucleotide-, pyruvate- and hormone-induced changes in pyruvate kinase activity in isolated rat hepatocytes. Biochem Biophys Res Commun. 1976 Oct 4;72(3):917–925. doi: 10.1016/s0006-291x(76)80219-7. [DOI] [PubMed] [Google Scholar]
  30. van de Werve G., Hue L., Hers H. G. Hormonal and ionic control of the glycogenolytic cascade in rat liver. Biochem J. 1977 Jan 15;162(1):135–142. doi: 10.1042/bj1620135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. van de Werve G., Stalmans W., Hers H. G. The effect of insulin on the glycogenolytic cascade and on the activity of glycogen synthase in the liver of anaesthetized rabbits. Biochem J. 1977 Jan 15;162(1):143–146. doi: 10.1042/bj1620143. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES