Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1988 Oct 15;255(2):507–512.

Vanadate raises fructose 2,6-bisphosphate concentrations and activates glycolysis in rat hepatocytes.

A M Gómez-Foix 1, J E Rodríguez-Gil 1, C Fillat 1, J J Guinovart 1, F Bosch 1
PMCID: PMC1135257  PMID: 2849417

Abstract

In rat hepatocytes, vanadate increases fructose 2,6-bisphosphate (Fru-2,6-P2) in a time- and dose-dependent manner, and counteracts the decrease in this metabolite caused by glucagon, forskolin or exogenous cyclic AMP. Vanadate does not directly modify the activity of 6-phosphofructo-2-kinase, even though it can counteract the inactivation of this enzyme caused by glucagon. Furthermore, vanadate raises the yield of 3H2O from [3-3H]glucose, indicating that it increases the flux through 6-phosphofructo-1-kinase. Moreover, vanadate in hepatocytes incubated in the presence of glucose increases the production of both lactate and CO2. Therefore vanadate has insulin-like effects on the glycolytic pathway in rat hepatocytes. These results clearly contrast with our previous observation that vanadate exerts glycogenolytic non-insulin-like effects on glycogen synthase and phosphorylase.

Full text

PDF
512

Selected References

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

  1. Bartrons R., Hue L., Van Schaftingen E., Hers H. G. Hormonal control of fructose 2,6-bisphosphate concentration in isolated rat hepatocytes. Biochem J. 1983 Sep 15;214(3):829–837. doi: 10.1042/bj2140829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Bosch F., Ariño J., Gómez-Foix A. M., Guinovart J. J. Glycogenolytic, noninsulin-like effects of vanadate on rat hepatocyte glycogen synthase and phosphorylase. J Biol Chem. 1987 Jan 5;262(1):218–222. [PubMed] [Google Scholar]
  4. Darfler F. J., Mahan L. C., Koachman A. M., Insel P. A. Stimulation of forskolin of intact S49 lymphoma cells involves the nucleotide regulatory protein of adenylate cyclase. J Biol Chem. 1982 Oct 25;257(20):11901–11907. [PubMed] [Google Scholar]
  5. Dubyak G. R., Kleinzeller A. The insulin-mimetic effects of vanadate in isolated rat adipocytes. Dissociation from effects of vanadate as a (Na+-K+)ATPase inhibitor. J Biol Chem. 1980 Jun 10;255(11):5306–5312. [PubMed] [Google Scholar]
  6. Gil J., Miralpeix M., Carreras J., Bartrons R. Insulin-like effects of vanadate on glucokinase activity and fructose 2,6-bisphosphate levels in the liver of diabetic rats. J Biol Chem. 1988 Feb 5;263(4):1868–1871. [PubMed] [Google Scholar]
  7. Heyliger C. E., Tahiliani A. G., McNeill J. H. Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats. Science. 1985 Mar 22;227(4693):1474–1477. doi: 10.1126/science.3156405. [DOI] [PubMed] [Google Scholar]
  8. Hue L., Bartrons R. Role of fructose 2,6-bisphosphate in the control by glucagon of gluconeogenesis from various precursors in isolated rat hepatocytes. Biochem J. 1984 Feb 15;218(1):165–170. doi: 10.1042/bj2180165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hue L., Blackmore P. F., Exton J. H. Fructose 2,6-bisphosphate. Hormonal regulation and mechanism of its formation in liver. J Biol Chem. 1981 Sep 10;256(17):8900–8903. [PubMed] [Google Scholar]
  10. Hue L., Rider M. H. Role of fructose 2,6-bisphosphate in the control of glycolysis in mammalian tissues. Biochem J. 1987 Jul 15;245(2):313–324. doi: 10.1042/bj2450313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Massagué J., Guinovart J. J. Insulin control of rat hepatocyte glycogen synthase and phosphorylase in the absence of glucose. FEBS Lett. 1977 Oct 15;82(2):317–320. doi: 10.1016/0014-5793(77)80610-8. [DOI] [PubMed] [Google Scholar]
  12. Matsutani A., Kaku K., Kaneko T. Tolbutamide stimulates fructose-2, 6-bisphosphate formation in perfused rat liver. Diabetes. 1984 May;33(5):495–498. doi: 10.2337/diab.33.5.495. [DOI] [PubMed] [Google Scholar]
  13. Meyerovitch J., Farfel Z., Sack J., Shechter Y. Oral administration of vanadate normalizes blood glucose levels in streptozotocin-treated rats. Characterization and mode of action. J Biol Chem. 1987 May 15;262(14):6658–6662. [PubMed] [Google Scholar]
  14. Monge L., Mojena M., Ortega J. L., Samper B., Cabello M. A., Feliu J. E. Chlorpropamide raises fructose-2,6-bisphosphate concentration and inhibits gluconeogenesis in isolated rat hepatocytes. Diabetes. 1986 Jan;35(1):89–96. doi: 10.2337/diab.35.1.89. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Richards C. S., Uyeda K. The effect of insulin and glucose on fructose-2,6-P2 in hepatocytes. Biochem Biophys Res Commun. 1982 Nov 30;109(2):394–401. doi: 10.1016/0006-291x(82)91734-x. [DOI] [PubMed] [Google Scholar]
  17. Shechter Y., Karlish S. J. Insulin-like stimulation of glucose oxidation in rat adipocytes by vanadyl (IV) ions. Nature. 1980 Apr 10;284(5756):556–558. doi: 10.1038/284556a0. [DOI] [PubMed] [Google Scholar]
  18. Tamura S., Brown T. A., Whipple J. H., Fujita-Yamaguchi Y., Dubler R. E., Cheng K., Larner J. A novel mechanism for the insulin-like effect of vanadate on glycogen synthase in rat adipocytes. J Biol Chem. 1984 May 25;259(10):6650–6658. [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. 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]

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

RESOURCES