Abstract
Treatment of rats with hypoglycaemic doses of hypoglycin has been shown to abolish the relative detritiation of [2-3H,U-14C]glucose [Osmundsen, Billington, Taylor & Sherratt (1978) Biochem. J. 170, 337-342], indicating that both the Cori and the glucose/glucose 6-phosphate cycles were inhibited in vivo. This inhibition was confirmed and, in addition, it was shown that the conversion in vivo of both [14C]lactate and [14C]fructose into glucose was decreased after hypoglycin treatment. These results suggest that hypoglycin poisoning results in the inhibition in vivo of glucose-6-phosphatase activity, which participates in the overall inhibition of gluconeogenesis and hypoglycaemia. Clofibrate feeding apparently protected the rats against the inhibition of the fructose-to-glucose conversion by hypoglycin. However, in isolated hepatocytes prepared from hypoglycin-treated rats, the conversion of [14C]fructose into glucose and the recycling of [2-3H,U-14C]glucose were not different from that in control hepatocytes. This suggests that the inhibition was lost during preparation of the hepatocytes. The direct measurement of glucose-6-phosphatase activity showed that it was inhibited when measured in concentrated, but not dilute, homogenates prepared from hypoglycin-treated rats.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arion W. J., Wallin B. K., Lange A. J., Ballas L. M. On the involvement of a glucose 6-phosphate transport system in the function of microsomal glucose 6-phosphatase. Mol Cell Biochem. 1975 Feb 28;6(2):75–83. doi: 10.1007/BF01732001. [DOI] [PubMed] [Google Scholar]
- Billington D., Sherratt H. S. Hypoglycin and metabolically related inhibitors. Methods Enzymol. 1981;72:610–616. doi: 10.1016/s0076-6879(81)72051-2. [DOI] [PubMed] [Google Scholar]
- 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]
- FENG P. C. Effect of hypoglycin A on the alpha cells of the pancreas. Nature. 1957 Oct 26;180(4591):855–856. doi: 10.1038/180855a0. [DOI] [PubMed] [Google Scholar]
- FENG P. C., PATRICK S. J. Studies of the action of hypoglycin-A, an hypoglycaemic substance. Br J Pharmacol Chemother. 1958 Jun;13(2):125–130. doi: 10.1111/j.1476-5381.1958.tb00206.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- Hue L., Hers H. G. On the use of (3H, 14C)labelled glucose in the study of the so-called "futile cycles" in liver and muscle. Biochem Biophys Res Commun. 1974 Jun 4;58(3):532–539. doi: 10.1016/s0006-291x(74)80453-5. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Nordlie R. C. Metabolic regulation by multifunctional glucose-6-phosphatase. Curr Top Cell Regul. 1974;8(0):33–117. doi: 10.1016/b978-0-12-152808-9.50009-2. [DOI] [PubMed] [Google Scholar]
- Osmundsen H., Billington D., Taylor J. R., Sherratt H. S. The effects of hypoglycin on glucose metabolism in the rat. A kinetic study in vivo and [U-14C,2-3H]glucose. Biochem J. 1978 Feb 15;170(2):337–342. doi: 10.1042/bj1700337. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sherratt H. S. Hypoglycin and related hypoglycaemic compounds. Br Med Bull. 1969 Sep;25(3):250–255. doi: 10.1093/oxfordjournals.bmb.a070713. [DOI] [PubMed] [Google Scholar]
- Tanaka K. On the mode of action of hypoglycin A. 3. Isolation and identification of cis-4-decene-1,10-dioic, cis, cis-4,7-decadiene-1,10-dioic, cis-4-octene-1,8-dioic, glutaric, and adipic acids, N-(methylenecyclopropyl)acetylglycine, and N-isovalerylglycine from urine of hypoglycin A-treated rats. J Biol Chem. 1972 Dec 10;247(23):7465–7478. [PubMed] [Google Scholar]
- Van Hoof F., Hue L., De Barsy T., Jacquemin P., Devos P., Hers H. G. Glycogen storage diseases. Biochimie. 1972;54(5):745–752. doi: 10.1016/s0300-9084(72)80177-9. [DOI] [PubMed] [Google Scholar]
- Van Hoof F., Hue L., Vamecq J., Sherratt H. S. Protection of rats by clofibrate against the hypoglycaemic and toxic effects of hypoglycin and pent-4-enoate. An ultrastructural and biochemical study. Biochem J. 1985 Jul 15;229(2):387–397. doi: 10.1042/bj2290387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- WOLLENBERGER A., RISTAU O., SCHOFFA G. [A simple technic for extremely rapid freezing of large pieces of tissue]. Pflugers Arch Gesamte Physiol Menschen Tiere. 1960;270:399–412. [PubMed] [Google Scholar]
- 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]
