Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1978 Jun 15;172(3):517–521. doi: 10.1042/bj1720517

Distinctive effects of glucagon on gluconeogenesis and ketogenesis in hepatocytes isolated from normal and biotin-deficient rats.

E A Siess, D G Brocks, O H Wieland
PMCID: PMC1185726  PMID: 687357

Abstract

In hepatocytes from 48 h-starved rats identical glucagon dose-response curves were obtained for the stimulation of gluconeogenesis from lactate, for ketogenesis and for the decreasing of the C5-dicarboxylate pool. Glucagon (20 nM) caused a 5-fold increase in 3-hydroxybutyrate formation, but decreased acetoacetate production 50% of that of the control. In hepatocytes from biotin-deficient rats glucagon no longer stimulated gluconeogenesis from lactate, but still produced its effects on the mitochondrial redox state and the C5-dicarboxylate pool. The results suggest that the primary site of the hormone action on gluconeogenesis is located within the mitochondria rather than in the cytosol.

Full text

PDF
517

Selected References

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

  1. Adam P. A., Haynes R. C., Jr Control of hepatic mitochondrial CO2 fixation by glucagon, epinephrine, and cortisol. J Biol Chem. 1969 Dec 10;244(23):6444–6450. [PubMed] [Google Scholar]
  2. Bewsher P. D., Ashmore J. Ketogenic and lipolytic effects of glucagon on liver. Biochem Biophys Res Commun. 1966 Aug 12;24(3):431–436. doi: 10.1016/0006-291x(66)90178-1. [DOI] [PubMed] [Google Scholar]
  3. Bhagavan H. N., Coursin D. B., Stewart C. N. Hypoglycemia in biotin deficiency. Life Sci. 1969 Mar 15;8(6):299–303. doi: 10.1016/0024-3205(69)90134-9. [DOI] [PubMed] [Google Scholar]
  4. Bryla J., Harris E. J., Plumb J. A. The stimulatory effect of glucagon and dibutyryl cyclic AMP on ureogenesis and gluconeogenesis in relation to the mitochondrial ATP content. FEBS Lett. 1977 Aug 15;80(2):443–448. doi: 10.1016/0014-5793(77)80494-8. [DOI] [PubMed] [Google Scholar]
  5. Böttger I., Wieland O., Brdiczka D., Pette D. Intracellular localization of pyruvate carboxylase and phosphoenolpyruvate carboxykinase in rat liver. Eur J Biochem. 1969 Mar;8(1):113–119. doi: 10.1111/j.1432-1033.1969.tb00503.x. [DOI] [PubMed] [Google Scholar]
  6. Claycomb W. C., Kilsheimer G. S. Effect of glucagon, adenosine-3',5'-monophosphate and theophylline on free fatty acid release by rat liver slices and on tissue levels of coenzyme A esters. Endocrinology. 1969 May;84(5):1179–1183. doi: 10.1210/endo-84-5-1179. [DOI] [PubMed] [Google Scholar]
  7. Cook G. A., Nielsen R. C., Hawkins R. A., Mehlman M. A., Lakshmanan M. R., Veech R. L. Effect of glucagon on hepatic malonyl coenzyme A concentration and on lipid synthesis. J Biol Chem. 1977 Jun 25;252(12):4421–4424. [PubMed] [Google Scholar]
  8. Deodhar A. D., Mistry S. P. Gluconeogenesis in biotin deficiency: in vivo synthesis of pyruvate holocarboxylase in biotin deficient rat liver. Biochem Biophys Res Commun. 1969 Mar 31;34(6):755–759. doi: 10.1016/0006-291x(69)90243-5. [DOI] [PubMed] [Google Scholar]
  9. Exton J. H., Corbin J. G., Park C. R. Control of gluconeogenesis in liver. IV. Differential effects of fatty acids and glucagon on ketogenesis and gluconeogenesis in the perfused rat liver. J Biol Chem. 1969 Aug 10;244(15):4095–4102. [PubMed] [Google Scholar]
  10. Fröhlich J., Wieland O. Glucagon and the permissive action of fatty acids in hepatic gluconeogenesis. Eur J Biochem. 1971 Apr 30;19(4):557–562. doi: 10.1111/j.1432-1033.1971.tb01349.x. [DOI] [PubMed] [Google Scholar]
  11. Johnson M. E., Das N. M., Butcher F. R., Fain J. N. The regulation of gluconeogenesis in isolated rat liver cells by glucagon, insulin, dibutyryl cyclic adenosine monophosphate, and fatty acids. J Biol Chem. 1972 May 25;247(10):3229–3235. [PubMed] [Google Scholar]
  12. Menahan L. A., Wieland O. Interactions of glucagon and insulin on the metabolism of perfused livers from fasted rats. Eur J Biochem. 1969 May 1;9(1):55–62. doi: 10.1111/j.1432-1033.1969.tb00575.x. [DOI] [PubMed] [Google Scholar]
  13. Patel M. S., Mistry S. P. Effect of sorbitol, fructose, succinate, aspartate, glutamate and fat on growth and survival time of biotin-deficient rats. J Nutr. 1968 Nov;96(3):409–414. doi: 10.1093/jn/96.3.409. [DOI] [PubMed] [Google Scholar]
  14. Ross B. D., Hems R., Freedland R. A., Krebs H. A. Carbohydrate metabolism of the perfused rat liver. Biochem J. 1967 Nov;105(2):869–875. doi: 10.1042/bj1050869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Siess E. A., Brocks D. G., Lattke H. K., Wieland O. H. Effect of glucagon on metabolite compartmentation in isolated rat liver cells during gluconeogenesis from lactate. Biochem J. 1977 Aug 15;166(2):225–235. doi: 10.1042/bj1660225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Siess E. A., Brocks D. G., Wieland O. H. Subcellular distribution of key metabolites in isolated liver cells from fasted rats. FEBS Lett. 1976 Oct 15;69(1):265–271. doi: 10.1016/0014-5793(76)80701-6. [DOI] [PubMed] [Google Scholar]
  18. Siess E. A., Wieland O. H. Improved response of isolated liver cells to glucagon in the presence of rat serum. Biochem Biophys Res Commun. 1975 May 5;64(1):323–330. doi: 10.1016/0006-291x(75)90256-9. [DOI] [PubMed] [Google Scholar]
  19. Struck E., Ashmore J., Wieland O. Effects of glucagon and long chain fatty acids on glucose production by isolated perfused rat liver. Adv Enzyme Regul. 1966;4:219–224. doi: 10.1016/0065-2571(66)90016-1. [DOI] [PubMed] [Google Scholar]
  20. Struck E., Ashmore J., Wieland O. Stimulierung der Gluconeogenese durch langkettige Fettsäuren und Glucagon. Biochem Z. 1965 Nov 5;343(1):107–110. [PubMed] [Google Scholar]
  21. Söling H. D., Willms B., Friedrichs D., Kleineke J. Regulation of gluconeogenesis by fatty acid oxidation in isolated perfused livers of non-starved rats. Eur J Biochem. 1968 Apr;4(3):364–372. doi: 10.1111/j.1432-1033.1968.tb00220.x. [DOI] [PubMed] [Google Scholar]
  22. Teufel H., Menahan L. A., Shipp J. C., Böning S., Wieland O. Effect of oleic acid on the oxidation and gluconeogenesis from [1-14C]pyruvate in the perfused rat liver. Eur J Biochem. 1967 Sep;2(2):182–186. doi: 10.1111/j.1432-1033.1967.tb00124.x. [DOI] [PubMed] [Google Scholar]
  23. Titheradge M. A., Coore H. G. The mitochondrial pyruvate carrier, its exchange properties and its regulation by glucagon. FEBS Lett. 1976 Mar 15;63(1):45–50. doi: 10.1016/0014-5793(76)80191-3. [DOI] [PubMed] [Google Scholar]
  24. Ui M., Claus T. H., Exton J. H., Park C. R. Studies on the mechanism of action of glucagon on gluconeogenesis. J Biol Chem. 1973 Aug 10;248(15):5344–5349. [PubMed] [Google Scholar]
  25. Ui M., Exton J. H., Park C. R. Effects of glucagon on glutamate metabolism in the perfused rat liver. J Biol Chem. 1973 Aug 10;248(15):5350–5359. [PubMed] [Google Scholar]
  26. Williamson D. H., Lund P., Krebs H. A. The redox state of free nicotinamide-adenine dinucleotide in the cytoplasm and mitochondria of rat liver. Biochem J. 1967 May;103(2):514–527. doi: 10.1042/bj1030514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Williamson J. R., Browning E. T., Scholz R. Control mechanisms of gluconeogenesis and ketogenesis. I. Effects of oleate on gluconeogenesis in perfused rat liver. J Biol Chem. 1969 Sep 10;244(17):4607–4616. [PubMed] [Google Scholar]
  28. Williamson J. R., Herczeg B., Coles H., Danish R. Studies on the ketogenic effect of glucagon in intact rat liver. Biochem Biophys Res Commun. 1966 Aug 12;24(3):437–442. doi: 10.1016/0006-291x(66)90179-3. [DOI] [PubMed] [Google Scholar]
  29. Williamson J. R., Kreisberg R. A., Felts P. W. Mechanism for the stimulation of gluconeogenesis by fatty acids in perfused rat liver. Proc Natl Acad Sci U S A. 1966 Jul;56(1):247–254. doi: 10.1073/pnas.56.1.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Williamson J. R., Scholz R., Browning E. T. Control mechanisms of gluconeogenesis and ketogenesis. II. Interactions between fatty acid oxidation and the citric acid cycle in perfused rat liver. J Biol Chem. 1969 Sep 10;244(17):4617–4627. [PubMed] [Google Scholar]
  31. Williamson J. R., Wright P. H., Malaisse W. J., Ashmore J. Control of gluconeogenesis by acetyl CoA in rats treated with glucagon and anti-insulin serum. Biochem Biophys Res Commun. 1966 Sep 8;24(5):765–770. doi: 10.1016/0006-291x(66)90391-3. [DOI] [PubMed] [Google Scholar]
  32. Yamazaki R. K. Glucagon stimulation of mitochondrial respiration. J Biol Chem. 1975 Oct 10;250(19):7924–7930. [PubMed] [Google Scholar]
  33. Yamazaki R. K., Sax R. D., Hauser M. A. Glucagon stimulation of mitochondrial ATPase and potassium ion transport. FEBS Lett. 1977 Mar 15;75(1):295–299. doi: 10.1016/0014-5793(77)80106-3. [DOI] [PubMed] [Google Scholar]

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

RESOURCES