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. 1996 Jan;64(1):108–112. doi: 10.1128/iai.64.1.108-112.1996

Endotoxin-induced enhancement of glucose influx into murine peritoneal macrophages via GLUT1.

M Fukuzumi 1, H Shinomiya 1, Y Shimizu 1, K Ohishi 1, S Utsumi 1
PMCID: PMC173734  PMID: 8557327

Abstract

Hypoglycemia is among the most injurious metabolic disorders caused by endotoxemia. In experimental endotoxemia with lipopolysaccharide (LPS) in animals, a marked glucose consumption is observed in macrophage-rich organs. However, the direct effect of LPS on the uptake of glucose by macrophages has not been fully understood, and the present study was undertaken to shed light on this point. The consumption and uptake of glucose, as measured with 2-deoxy-D-[3H]glucose, by murine peritoneal exudate macrophages in culture were accelerated two- to threefold by stimulation with 3 ng of LPS per ml. The rate of glucose uptake reached a plateau after 20 min of stimulation and remained at the maximum as long as LPS was present. Northern (RNA) blot analysis with cDNA probes for five known isoforms of glucose transporter (GLUT) revealed that the expression of GLUT by macrophages was restricted to the GLUT1 isoform during LPS stimulation and the amount of GLUT1 mRNA was increased by the stimulation. These results suggest that macrophage responses to LPS are supported by a rapid and sustained glucose influx via GLUT1 and that this is a participating factor in the development of systemic hypoglycemia when endotoxemia is prolonged.

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Selected References

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  1. Ardawi M. S., Newsholme E. A. Metabolism in lymphocytes and its importance in the immune response. Essays Biochem. 1985;21:1–44. [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. Bone R. C., Fisher C. J., Jr, Clemmer T. P., Slotman G. J., Metz C. A., Balk R. A. A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med. 1987 Sep 10;317(11):653–658. doi: 10.1056/NEJM198709103171101. [DOI] [PubMed] [Google Scholar]
  4. Chakrabarti R., Jung C. Y., Lee T. P., Liu H., Mookerjee B. K. Changes in glucose transport and transporter isoforms during the activation of human peripheral blood lymphocytes by phytohemagglutinin. J Immunol. 1994 Mar 15;152(6):2660–2668. [PubMed] [Google Scholar]
  5. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  6. Filkins J. P. Phases of glucose dyshomeostasis in endotoxicosis. Circ Shock. 1978;5(4):347–355. [PubMed] [Google Scholar]
  7. Fischer K. F., Lees J. A., Newman J. H. Hypoglycemia in hospitalized patients. Causes and outcomes. N Engl J Med. 1986 Nov 13;315(20):1245–1250. doi: 10.1056/NEJM198611133152002. [DOI] [PubMed] [Google Scholar]
  8. Freudenberg M. A., Freudenberg N., Galanos C. Time course of cellular distribution of endotoxin in liver, lungs and kidneys of rats. Br J Exp Pathol. 1982 Feb;63(1):56–65. [PMC free article] [PubMed] [Google Scholar]
  9. Gould G. W., Bell G. I. Facilitative glucose transporters: an expanding family. Trends Biochem Sci. 1990 Jan;15(1):18–23. doi: 10.1016/0968-0004(90)90125-u. [DOI] [PubMed] [Google Scholar]
  10. Kreger B. E., Craven D. E., McCabe W. R. Gram-negative bacteremia. IV. Re-evaluation of clinical features and treatment in 612 patients. Am J Med. 1980 Mar;68(3):344–355. doi: 10.1016/0002-9343(80)90102-3. [DOI] [PubMed] [Google Scholar]
  11. Lang C. H., Bagby G. J., Spitzer J. J. Glucose kinetics and body temperature after lethal and nonlethal doses of endotoxin. Am J Physiol. 1985 Apr;248(4 Pt 2):R471–R478. doi: 10.1152/ajpregu.1985.248.4.R471. [DOI] [PubMed] [Google Scholar]
  12. Lang C. H., Dobrescu C. Gram-negative infection increases noninsulin-mediated glucose disposal. Endocrinology. 1991 Feb;128(2):645–653. doi: 10.1210/endo-128-2-645. [DOI] [PubMed] [Google Scholar]
  13. Lang C. H., Dobrescu C. Sepsis-induced increases in glucose uptake by macrophage-rich tissues persist during hypoglycemia. Metabolism. 1991 Jun;40(6):585–593. doi: 10.1016/0026-0495(91)90048-2. [DOI] [PubMed] [Google Scholar]
  14. Mathison J. C., Ulevitch R. J. The clearance, tissue distribution, and cellular localization of intravenously injected lipopolysaccharide in rabbits. J Immunol. 1979 Nov;123(5):2133–2143. [PubMed] [Google Scholar]
  15. Miller S. I., Wallace R. J., Jr, Musher D. M., Septimus E. J., Kohl S., Baughn R. E. Hypoglycemia as a manifestation of sepsis. Am J Med. 1980 May;68(5):649–654. doi: 10.1016/0002-9343(80)90250-8. [DOI] [PubMed] [Google Scholar]
  16. Morrison D. C., Ryan J. L. Bacterial endotoxins and host immune responses. Adv Immunol. 1979;28:293–450. doi: 10.1016/s0065-2776(08)60802-0. [DOI] [PubMed] [Google Scholar]
  17. Mészáros K., Lang C. H., Bagby G. J., Spitzer J. J. Contribution of different organs to increased glucose consumption after endotoxin administration. J Biol Chem. 1987 Aug 15;262(23):10965–10970. [PubMed] [Google Scholar]
  18. Orlinska U., Newton R. C. Role of glucose in interleukin-1 beta production by lipopolysaccharide-activated human monocytes. J Cell Physiol. 1993 Oct;157(1):201–208. doi: 10.1002/jcp.1041570126. [DOI] [PubMed] [Google Scholar]
  19. Qi M., Jones S. B. Contribution of platelet activating factor to hemodynamic and sympathetic responses to bacterial endotoxin in conscious rats. Circ Shock. 1990 Oct;32(2):153–163. [PubMed] [Google Scholar]
  20. Saiki R. K., Scharf S., Faloona F., Mullis K. B., Horn G. T., Erlich H. A., Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350–1354. doi: 10.1126/science.2999980. [DOI] [PubMed] [Google Scholar]
  21. Shimizu Y., Kielar D., Masuno H., Minokoshi Y., Shimazu T. Dexamethasone induces the GLUT4 glucose transporter, and responses of glucose transport to norepinephrine and insulin in primary cultures of brown adipocytes. J Biochem. 1994 Jun;115(6):1069–1074. doi: 10.1093/oxfordjournals.jbchem.a124459. [DOI] [PubMed] [Google Scholar]
  22. Shinomiya H., Hagi A., Fukuzumi M., Mizobuchi M., Hirata H., Utsumi S. Complete primary structure and phosphorylation site of the 65-kDa macrophage protein phosphorylated by stimulation with bacterial lipopolysaccharide. J Immunol. 1995 Apr 1;154(7):3471–3478. [PubMed] [Google Scholar]
  23. Shinomiya H., Hirata H., Nakano M. Purification and characterization of the 65-kDa protein phosphorylated in murine macrophages by stimulation with bacterial lipopolysaccharide. J Immunol. 1991 May 15;146(10):3617–3625. [PubMed] [Google Scholar]
  24. Spolarics Z., Bagby G. J., Lang C. H., Spitzer J. J. Up-regulation of glucose metabolism in Kupffer cells following infusion of tumour necrosis factor. Biochem J. 1991 Sep 1;278(Pt 2):515–519. doi: 10.1042/bj2780515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Suzue K., Lodish H. F., Thorens B. Sequence of the mouse liver glucose transporter. Nucleic Acids Res. 1989 Dec 11;17(23):10099–10099. doi: 10.1093/nar/17.23.10099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Yelich M. R. Effects of endotoxin and interleukin-1 on glucagon and insulin secretion from the perfused rat pancreas. Pancreas. 1992;7(3):358–366. doi: 10.1097/00006676-199205000-00014. [DOI] [PubMed] [Google Scholar]
  27. Zeller W. P., The S. M., Sweet M., Goto M., Gottschalk M. E., Hurley R. M., Filkins J. P., Hofmann C. Altered glucose transporter mRNA abundance in a rat model of endotoxic shock. Biochem Biophys Res Commun. 1991 Apr 15;176(1):535–540. doi: 10.1016/0006-291x(91)90958-a. [DOI] [PubMed] [Google Scholar]
  28. Ziegler E. J., Fisher C. J., Jr, Sprung C. L., Straube R. C., Sadoff J. C., Foulke G. E., Wortel C. H., Fink M. P., Dellinger R. P., Teng N. N. Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group. N Engl J Med. 1991 Feb 14;324(7):429–436. doi: 10.1056/NEJM199102143240701. [DOI] [PubMed] [Google Scholar]

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