AMPK in Health and Disease.
Steinberg GR, Kemp BE Physiol Rev 2009; 89:1025-78
Protein Chemistry and Metabolism, St. Vincent's Institute of Medical Research, University of Melbourne, Fitzroy, Victoria, Australia.
Regulation of energy and protein homeostasis is of utmost importance
for maintaining health in an insulted organism. In life-threatening
situations as in sepsis or polytrauma, multifactorial endogenous and
exogenous strategies are needed for survival. However, our treatment
modalities during the past 20 years seem to be less effective because
during this time mortality rates of 40-60% of patients with severe
sepsis (including septic shock) have not changed significantly (Engel C; Intensive Care Med 2007; 33:606).
Therefore, we have to re-evaluate our strategies, looking forward for
new interventions and concepts. Possibly, a better understanding of
endogenous processes in stressed cells may help to define better
treatment modalities in severely ill patients.
Sepsis is characterised by an inflammatory response to infection which mediates several metabolic pathways such as energy production and protein catabolism. Peripheral protein catabolism caused by stimulated protein degradation and attenuated protein synthesis assists to deliver metabolites from the skeletal muscle to central organs to ensure glucose delivery to glucose dependent organs (central nervous system, erythrocytes, tissue repair) and amino acids supply for synthesis of proteins needed for inflammation response. This centralisation of the metabolism is partly mediated by endotoxin and cytokines, which are necessary and positive regulators of the insulted organism at least during the onset of the inflammatory response. AMPK-signalling seems to be of outstanding importance in regulation of cellular and whole body energy balance.
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