How does blood glucose control with insulin save lives in intensive care?
Greet Van den Berghe
Greet Van den Berghe
Published November 1, 2004
Citation Information: J Clin Invest. 2004;114(9):1187-1195. https://doi.org/10.1172/JCI23506.
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How does blood glucose control with insulin save lives in intensive care?

Abstract

Patients requiring prolonged intensive care are at high risk for multiple organ failure and death. Insulin resistance and hyperglycemia accompany critical illness, and the severity of this “diabetes of stress” reflects the risk of death. Recently it was shown that preventing hyperglycemia with insulin substantially improves outcome of critical illness. This article examines some potential mechanisms underlying prevention of glucose toxicity as well as the effects of insulin independent of glucose control. Unraveling the molecular mechanisms will provide new insights into the pathogenesis of multiple organ failure and open avenues for novel therapeutic strategies.

Authors

Greet Van den Berghe

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Figure 3

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A diagrammatic representation of energy production in mitochondria and t...
A diagrammatic representation of energy production in mitochondria and the mechanism of peroxynitrite generation. Excessive glycolysis and oxidative phosphorylation may result in more peroxynitrite generation in the critically ill. The ensuing nitration of mitochondrial complexes I and IV, MnSOD, GAPDH, and VDAC may suppress the activity of the mitochondrial electron transfer chain, impair detoxification of superoxide, shuttle glucose into toxic pathways, and increase apoptosis, respectively. These toxic effects may explain organ and cellular system failure related to adverse outcome in the critically ill. Proteins that are nitrated are indicated by the letter N in a yellow circle. Figure adapted with permission from American journal of physiology. Heart and circulatory physiology (44). TCA, tricarboxylic acid cycle; CoQ, coenzyme Q; Cyt c, cytochrome c; mtNOS, mitochondrial NO synthase; ANT, adenine nucleotide translocase; SCOT, succinyl-CoA:3-oxoacid CoA-transferase, ONOO–, peroxynitrite; F0, the portion of the mitochondrial ATP synthase that channels protons through the membrane.