The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Intensive insulin therapy protects the endothelium of critically ill patients
Open accessAbstract
The vascular endothelium controls vasomotor tone and microvascular flow and regulates trafficking of nutrients and biologically active molecules. When endothelial activation is excessive, compromised microcirculation and subsequent cellular hypoxia contribute to the risk of organ failure. We hypothesized that strict blood glucose control with insulin during critical illness protects the endothelium, mediating prevention of organ failure and death. In this preplanned subanalysis of a large, randomized controlled study, intensive insulin therapy lowered circulating levels of ICAM-1 and tended to reduce E-selectin levels in patients with prolonged critical illness, which reflects reduced endothelial activation. This effect was not brought about by altered levels of endothelial stimuli, such as cytokines or VEGF, or by upregulation of eNOS. In contrast, prevention of hyperglycemia by intensive insulin therapy suppressed iNOS gene expression in postmortem liver and skeletal muscle, possibly in part via reduced NF-kappaB activation, and lowered the elevated circulating NO levels in both survivors and nonsurvivors. These effects on the endothelium statistically explained a significant part of the improved patient outcome with intensive insulin therapy. In conclusion, maintaining normoglycemia with intensive insulin therapy during critical illness protects the endothelium, likely in part via inhibition of excessive iNOS-induced NO release, and thereby contributes to prevention of organ failure and death.
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The biology of VEGF and its receptors
Ferrara, N., Gerber, H.-P., & LeCouter, J. (2003) · Nature Medicine · doi:10.1038/nm0603-669 · Cited by 9,591
Biochemistry and molecular cell biology of diabetic complications
Brownlee, M. (2001) · Nature · doi:10.1038/414813a · Cited by 9,107
Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation
Dimmeler, S., Fleming, I., Fisslthaler, B., Hermann, C., Busse, R., & Zeiher, A. M. (1999) · Nature · doi:10.1038/21224 · Cited by 3,591
Pathogenetic Mechanisms of Septic Shock
Epstein, F. H., & Parrillo, J. E. (1993) · New England Journal of Medicine · doi:10.1056/nejm199305203282008 · Cited by 1,548
Tonnesen, M. G., Feng, X., & Clark, R. A. F. (2000) · Journal of Investigative Dermatology Symposium Proceedings · doi:10.1046/j.1087-0024.2000.00014.x · Cited by 1,463
Cusi, K., Maezono, K., Osman, A., Pendergrass, M., Patti, M. E., Pratipanawatr, T., DeFronzo, R. A., Kahn, C. R., & Mandarino, L. J. (2000) · Journal of Clinical Investigation · doi:10.1172/jci7535 · Cited by 1,139
Increased mortality associated with growth hormone treatment in critically ill adults
Takala, J., Ruokonen, E., Webster, N. R., Nielsen, M. S., Zandstra, D. F., Vundelinckx, G., & Hinds, C. J. (1999) · New England Journal of Medicine · doi:10.1056/nejm199909093411102 · Cited by 1,023
Cited by
Intensive insulin therapy in the medical ICU
Van den Berghe, G., Wilmer, A., Hermans, G., Meersseman, W., Wouters, P. J., Milants, I., Van Wijngaerden, E., Bobbaers, H., & Bouillon, R. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa052521 · Cited by 3,639
ESPEN guidelines on parenteral nutrition: intensive care
Singer, P., Berger, M. M., Van den Berghe, G., Biolo, G., Calder, P., Forbes, A., Griffiths, R., Kreyman, G., Leverve, X., & Pichard, C. (2009) · Clinical Nutrition · doi:10.1016/j.clnu.2009.04.024 · Cited by 1,907
Authors/Task Force Members, Ryden, L., Standl, E., Bartnik, M., Van den Berghe, G., Betteridge, J., de Boer, M.-J., Cosentino, F., Jonsson, B., Laakso, M., et al. (2006) · European Heart Journal · doi:10.1093/eurheartj/ehl260 · Cited by 1,647
Dungan, K. M., Braithwaite, S. S., & Preiser, J.-C. (2009) · The Lancet · doi:10.1016/s0140-6736(09)60553-5 · Cited by 1,431
Yu, T., Robotham, J. L., & Yoon, Y. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0511154103 · Cited by 1,246
Metadata
- Authors
- Langouche, L.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-08-01
- Volume
- 115
- Issue
- 8
- Pages
- 2277-2286
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2117520303
- Cited by
- 467
- References
- 7
- FWCI
- 34.66
- Type
- journal article
- Language
- en
- Open access
- bronze
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