Progressive cellular dehydration and proteolysis in critically ill patients

Finn, Patrick; Plank, Lindsay D.; Clark, Matthew A.; Connolly, Andrew B.; Hill, Graham L.

doi:10.1016/s0140-6736(96)91204-0

Cited by 138 publications

(77 citation statements)

References 17 publications

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“…However, it suggests that improvement in cellular hydration may affect protein anabolism. Finn et al (1996) have studied critically ill patients (nine trauma and 11 sepsis). They measured water compartments every 5 days during 21 days, and total body protein and total body potassium with state-of-the-art techniques (including in vivo neutron activation analysis).…”

Section: Changes In Water Compartments In Diseased Humansmentioning

confidence: 99%

Effects of changes in water compartments on physiology and metabolism

et al. 2003

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There is paramount evidence to suggest the importance of cell volume changes for the regulation of cell function, including protein metabolism. Among many other effects, cell swelling inhibits proteolysis and stimulates protein synthesis. However, most of the data pertinent to this theory relate to in vitro experiments. This paper reviews the evidence about the relevance of cell swelling and changes in water compartments to regulation of metabolism at the whole body level in animals and humans. Protein metabolism is most likely regulated by cellular hydration in health and disease. Cellular hydration appears to bear no effect on energy metabolism. The relationship between cellular hydration and lipolysis deserves to be verified. There appears to be a possible weak effect on glucose metabolism. Further studies are therefore necessary to challenge the cell swelling theory. If confirmed, strategies to modify cellular hydration could be used to improve metabolic orientations especially in the critically ill.

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Section: Changes In Water Compartments In Diseased Humansmentioning

confidence: 99%

Effects of changes in water compartments on physiology and metabolism

et al. 2003

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“…The importance of cell volume in the control of proteolysis in vivo is highlighted by the observation that in a large number of clinical patients the cellular hydration state of skeletal muscle was inversely correlated with the degree of nitrogen loss from this tissue (Häussinger et al, 1993;Finn et al, 1996). Significantly, cell swelling, like insulin, promotes transport of glutamine into muscle cells, whereas cell shrinkage has the opposite effect (Low et al, 1996).…”

Section: Control By Amino Acids and Hormonesmentioning

confidence: 99%

Untitled

Blommaart

1997

The Histochemical Journal

204

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SummaryThe rate of proteolysis is an important determinant of the intracellular protein content. Part of the degradation of intracellular proteins occurs in the lysosomes and is mediated by macroautophagy. In liver, macroautophagy is very active and almost completely accounts for starvation-induced proteolysis. Factors inhibiting this process include amino acids, cell swelling and insulin. In the mechanisms controlling macroautophagy, protein phosphorylation plays an important role. Activation of a signal transduction pathway, ultimately leading to phosphorylation of ribosomal protein S6, accompanies inhibition of macroautophagy. Components of this pathway may include a heterotrimeric G i3 -protein, phosphatidylinositol 3-kinase and p70S6 kinase. Recent evidence indicates that lysosomal protein degradation can be selective and occurs via ubiquitin-dependent and -independent pathways.

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“…Dehydration in decompensated diabetes mellitus-a model of hyperosmolality-is associated with protein catabolism and insulin resistance of glucose metabolism (Hellerstein, 1995). Further, critically ill patients demonstrated progressive cellular dehydration associated with proteolysis (Finn et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Effects of changes in hydration on protein, glucose and lipid metabolism in man: impact on health

Keller¹,

Szinnai

Bilz³

et al. 2003

Eur J Clin Nutr

101

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Alterations of cell volume induced by changes of extracellular osmolality have been reported to regulate intracellular metabolic pathways. Hypo-osmotic cell swelling counteracts proteolysis and glycogen breakdown in the liver, whereas hyperosmotic cell shrinkage promotes protein breakdown, glycolysis and glycogenolysis. To investigate the effect of acute changes of extracellular osmolality on whole-body protein, glucose and lipid metabolism in vivo, we studied 10 male subjects during three conditions: (i) hyperosmolality was induced by fluid restriction and intravenous infusion of hypertonic NaCl (2-5%, wt/vol) during 17 h; (ii) hypo-osmolality was produced by intravenous administration of desmopressin, liberal water drinking and infusion of hypotonic saline (0.4%); and (iii) the iso-osmolality study comprised oral water intake ad libitum. Plasma osmolality increased from 28571 to 29671 mosm/kg (Po0.001during hyperosmolality, and decreased from 28671 to 26571 mosm/kg during hypo-osmolality (Po0.001). Total body leucine flux ([1-13 C]leucine infusion technique), reflecting whole-body protein breakdown, as well as whole-body leucine oxidation rate (irreversible loss of amino acids) decreased significantly during hypo-osmolality. The glucose metabolic clearance rate during hyperinsulinaemic-euglycemic clamping increased significantly less during hypo-osmolality than iso-osmolality, indicating diminished peripheral insulin sensitivity. Glycerol turnover (2-[ 13 C]glycerol infusion technique), reflecting whole-body lipolysis, increased significantly during hypo-osmolar conditions. The results demonstrate that the metabolic adaptation to acute hypo-osmolality resembles that of acute fasting, that is, it results in protein sparing associated with increased lipolysis, ketogenesis and lipid oxidation and impaired insulin sensitivity of glucose metabolism.

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Progressive cellular dehydration and proteolysis in critically ill patients

Cited by 138 publications

References 17 publications

Effects of changes in water compartments on physiology and metabolism

Effects of changes in water compartments on physiology and metabolism

Untitled

Effects of changes in hydration on protein, glucose and lipid metabolism in man: impact on health

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