Intensive Care Medicine

, Volume 29, Issue 4, pp 642–645 | Cite as

High glucose impairs superoxide production from isolated blood neutrophils

Experimental

Abstract

Objective

Superoxide (O2), a key antimicrobial agent in phagocytes, is produced by the activity of NADPH oxidase. High glucose concentrations may, however, impair the production of O2 through inhibition of glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the formation of NADPH. This study measured the acute effects of high glucose or the G6PD inhibitor dehydroepiandrosterone (DHEA) on the production of O2 from isolated human neutrophils.

Design

Laboratory studies of short-term cultures of neutrophil granulocytes.

Participants

Healthy subjects.

Interventions

Neutrophils were isolated from peripheral blood and incubated for 1 h in Krebs-Ringer buffer containing 5, 10, or 25 mM glucose, 5 mM glucose with 0, 5, or 20 mM mannitol, or 5 mM glucose with 0, 1, 10, or 100 µM DHEA. O2 production was induced by N-formyl-methionyl-leucyl-phenylalanine and measured by the cytochrome c reduction assay. Potential scavenging of O2 by glucose, mannitol, or DHEA was assessed in a cell free system using the pyrogallol assay.

Measurements and results

Incubation of neutrophils with glucose dose-dependently reduced O2 production, which was 50% decreased at 25 mM glucose. Also DHEA reduced the production of O2 dose-dependently, whereas production rates were unaffected by mannitol. Neither glucose, mannitol, nor DHEA scavenged O2.

Conclusions

High extracellular glucose concentrations acutely reduce O2 production from activated neutrophils possibly through inhibition of G6PD. If this occurs in vivo, microbial killing by neutrophils may be impaired during acute hyperglycemia, as observed after major surgery, trauma, or severe infection.

Keywords

Glucose Glucose-phosphate dehydrogenase Neutrophils Reactive oxygen species Superoxides 

References

  1. 1.
    Berghe G van den, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R (2001) Intensive insulin therapy in the surgical intensive care unit. N Engl J Med 345:1359–1367PubMedGoogle Scholar
  2. 2.
    Nielson CP, Hindson DA (1989) Inhibition of polymorphonuclear leukocyte respiratory burst by elevated glucose concentrations in vitro. Diabetes 38:1031–1035PubMedGoogle Scholar
  3. 3.
    Zhang Z, Apse K, Pang J, Stanton RC (2000) High glucose inhibits glucose-6-phosphate dehydrogenase via cAMP in aortic endothelial cells. J Biol Chem 275:40042–40047CrossRefPubMedGoogle Scholar
  4. 4.
    Perner A, Andresen L, Pedersen G, Rask-Madsen J (2003) Superoxide production and expression of NAD(P) H oxidases by transformed and primary human colonic epithelial cells. Gut 52:233–238Google Scholar
  5. 5.
    Plevak DJ, Southorn PA, Narr BJ, Peters SG (1989) Intensive-care unit experience in the Mayo liver transplantation program: the first 100 cases. Mayo Clin Proc 64:433–445PubMedGoogle Scholar
  6. 6.
    Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474PubMedGoogle Scholar
  7. 7.
    Winkelstein JA, Marino MC, Johnston RBJ, Boyle J, Curnutte J, Gallin JI, Malech HL, Holland SM, Ochs H, Quie P, Buckley RH, Foster CB, Chanock SJ, Dickler H (2000) Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore) 79:155–169Google Scholar
  8. 8.
    Fietsam R Jr, Bassett J, Glover JL (1991) Complications of coronary artery surgery in diabetic patients. Am Surg 57:551–557PubMedGoogle Scholar
  9. 9.
    Gallacher SJ, Thomson G, Fraser WD, Fisher BM, Gemmell CG, MacCuish AC (1995) Neutrophil bactericidal function in diabetes mellitus: evidence for association with blood glucose control. Diabet Med 12:916–920PubMedGoogle Scholar
  10. 10.
    Rassias AJ, Marrin CA, Arruda J, Whalen PK, Beach M, Yeager MP (1999) Insulin infusion improves neutrophil function in diabetic cardiac surgery patients. Anesth Analg 88:1011–1016PubMedGoogle Scholar
  11. 11.
    Bagdade JD, Root RK, Bulger RJ (1974) Impaired leukocyte function in patients with poorly controlled diabetes. Diabetes 23:9–15PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  1. 1.Department of Anesthesia and Intensive Care 4132RigshospitaletCopenhagenDenmark
  2. 2.Department of Gastroenterology, Herlev HospitalUniversity of CopenhagenDenmark

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