Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1983 Jan;39(1):213–219. doi: 10.1128/iai.39.1.213-219.1983

Influence of endotoxin treatment on dexamethasone induction of hepatic phosphoenolpyruvate carboxykinase.

R E McCallum, T W Seale, R D Stith
PMCID: PMC347928  PMID: 6822414

Abstract

Decreased glucocorticoid binding has been observed at a time after endotoxin (3 to 6 h) when imparied liver enzyme induction is known to occur. This study was undertaken to characterize the early time course of hypoglycemia and decreased liver phosphoenolpyruvate carboxykinase (PEPCK) activity in intact and adrenalectomized mice given endotoxin. In addition, altered steroid induction of hepatic PEPCK was examined in adrenalectomized mice given dexamethasone at intervals before and after a median lethal dose of endotoxin. Intact mice demonstrated a dramatic hyperglycemia at 1 h after endotoxin treatment, a response absent in adrenalectomized mice. Plasma glucose levels were significantly reduced from control values at 3 and 6 h posttreatment, with the most pronounced endotoxin-induced hypoglycemia seen in adrenalectomized mice. Hepatic PEPCK activity in intact mice given endotoxin was decreased at 3 and 6 h after treatment, although no change from basal, noninduced levels was seen in poisoned adrenalectomized mice. The increased increment in hepatic PEPCK activity due to fasting of intact control mice was reproduced in adrenalectomized control mice by the administration of dexamethasone. Furthermore, the induction of hepatic PEPCK by dexamethasone was inhibited by 1 h after endotoxin treatment, with enzyme activity falling to basal, noninduced levels by 6 h posttreatment. At these same time intervals after endotoxin treatment, no evidence of histopathology in the liver or adrenal glands was seen. These results coincide with changes in steroid binding seen previously and indicate that endotoxin treatment produces significant alterations in glucocorticoid action at the subcellular or molecular level.

Full text

PDF
213

Selected References

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

  1. BERRY L. J., SMYTHE D. S. EFFECTS OF BACTERIAL ENDOTOXINS ON METABOLISM. VI. THE ROLE OF TRYPTOPHAN PYRROLASE IN RESPONSE OF MICE TO ENDOTOXIN. J Exp Med. 1963 Oct 1;118:587–603. doi: 10.1084/jem.118.4.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berk J. L., Hagen J. F., Beyer W. H., Gerber M. J. Hypoglycemia of shock. Ann Surg. 1970 Mar;171(3):400–408. doi: 10.1097/00000658-197003000-00013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berry L. J. Bacterial toxins. CRC Crit Rev Toxicol. 1977 Nov;5(3):239–318. doi: 10.3109/10408447709082601. [DOI] [PubMed] [Google Scholar]
  4. Berry L. J., Smythe D. S., Colwell L. S. Inhibition of hepatic enzyme induction as a sensitive assay for endotoxin. J Bacteriol. 1968 Oct;96(4):1191–1199. doi: 10.1128/jb.96.4.1191-1199.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  6. Chang H. C., Lane M. D. The enzymatic carboxylation of phosphoenolpyruvate. II. Purification and properties of liver mitochondrial phosphoenolpyruvate carboxykinase. J Biol Chem. 1966 May 25;241(10):2413–2420. [PubMed] [Google Scholar]
  7. Exton J. H. Gluconeogenesis. Metabolism. 1972 Oct;21(10):945–990. doi: 10.1016/0026-0495(72)90028-5. [DOI] [PubMed] [Google Scholar]
  8. Filkins J. P., Cornell R. P. Depression of hepatic gluconeogenesis and the hypoglycemia of endotoxin shock. Am J Physiol. 1974 Oct;227(4):778–781. doi: 10.1152/ajplegacy.1974.227.4.778. [DOI] [PubMed] [Google Scholar]
  9. Foster D. O., Ray P. D., Lardy H. A. Studies on the mechanisms underlying adaptive changes in rat liver phosphoenolpyruvate carboxykinase. Biochemistry. 1966 Feb;5(2):555–562. doi: 10.1021/bi00866a022. [DOI] [PubMed] [Google Scholar]
  10. Hanson R. W., Garber A. J. Phosphoenolpyruvate carboxykinase. I. Its role in gluconeogenesis. Am J Clin Nutr. 1972 Oct;25(10):1010–1021. doi: 10.1093/ajcn/25.10.1010. [DOI] [PubMed] [Google Scholar]
  11. Hinshaw L. B., Peyton M. D., Archer L. T., Black M. R., Coalson J. J., Greenfield L. J. Prevention of death in endotoxin shock by glucose administration. Surg Gynecol Obstet. 1974 Dec;139(6):851–859. [PubMed] [Google Scholar]
  12. LaNoue K. F., Mason A. D., Jr, Daniels J. P. The impairment of glucogenesis by gram negative infection. Metabolism. 1968 Jul;17(7):606–611. doi: 10.1016/0026-0495(68)90019-x. [DOI] [PubMed] [Google Scholar]
  13. Lau T. S., Taubenfligel W., Levene R., Farago G., Chan H., Koven I., Drucker W. R. Pancreatic blood flow and insulin output in severe hemorrhage. J Trauma. 1972 Oct;12(10):880–884. doi: 10.1097/00005373-197210000-00008. [DOI] [PubMed] [Google Scholar]
  14. McCallum R. E., Berry L. J. Effects of endotoxin on gluconeogenesis, glycogen synthesis, and liver glycogen synthase in mice. Infect Immun. 1973 Apr;7(4):642–654. doi: 10.1128/iai.7.4.642-654.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McCallum R. E. Hepatocyte-Kupffer cell interactions in the inhibition of hepatic gluconeogenesis by bacterial endotoxin. Prog Clin Biol Res. 1981;62:99–113. [PubMed] [Google Scholar]
  16. McCallum R. E., Stith R. D. Endotoxin-induced inhibition of steroid binding by mouse liver cytosol. Circ Shock. 1982;9(4):357–367. [PubMed] [Google Scholar]
  17. Moore R. N., Berry L. J. Inhibited hormonal induction of hepatic phosphoenolpyruvate carboxykinase in poly I: treated mice, an endotoxin-like glucocorticoid antagonism. Experientia. 1976 Dec 15;32(12):1566–1568. doi: 10.1007/BF01924457. [DOI] [PubMed] [Google Scholar]
  18. Phillips L. J., Berry L. J. Hormonal control of mouse liver phosphoenolpyruvate carboxykinase rhythm. Am J Physiol. 1970 Sep;219(3):697–701. doi: 10.1152/ajplegacy.1970.219.3.697. [DOI] [PubMed] [Google Scholar]
  19. Rippe D. F., Berry L. J. Immunological quantitation of hepatic tryptophan oxygenase in endotoxin-poisoned mice. Infect Immun. 1973 Oct;8(4):534–539. doi: 10.1128/iai.8.4.534-539.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rippe D. F., Berry L. J. Study of inhibition of induction of phosphoenolpyruvate carboxykinase by endotoxin with radial immunodiffusion. Infect Immun. 1972 Nov;6(5):766–772. doi: 10.1128/iai.6.5.766-772.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Shands J. W., Jr, Miller V., Martin H., Senterfitt V. Hypoglycemic activity of endotoxin. II. Mechanism of the phenomenon in BCG-infected mice. J Bacteriol. 1969 May;98(2):494–501. doi: 10.1128/jb.98.2.494-501.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Shands J. W., Jr, Miller V., Martin H. The hypoglycemic activity of endotoxin. I. Occurrence in animals hyperreactive to endotoxin. Proc Soc Exp Biol Med. 1969 Feb;130(2):413–417. doi: 10.3181/00379727-130-33568. [DOI] [PubMed] [Google Scholar]
  23. Tavakoli H., Moon R. J. In vitro interactions of endotoxin, chromatin, DNA, and steroid hormone receptors. Prog Clin Biol Res. 1981;62:33–43. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES