Patients with chronic HF (heart failure) experience muscle atrophy during the course of the disease. The mechanisms underlying muscle atrophy in HF, however, are not understood. Thus we evaluated leg phenylalanine balance and kinetics in HF patients and controls following a brief fast (24 h) and under euglycaemic–hyperinsulinaemic–hyperaminoacidaemic conditions to determine whether HF increases muscle protein catabolism in response to nutritional deprivation and/or diminishes the anabolic response to meal-related stimuli (insulin and amino acids) and whether alterations in protein metabolism correlate to circulating cytokine levels. No differences in phenylalanine balance, rate of appearance or rate of disappearance were found between patients and controls under fasting conditions. However, the anabolic response to hyperinsulinaemia–hyperaminoacidaemia was reduced by more than 50% in patients compared with controls. The diminished anabolic response was due to reduced suppression of the leg phenylalanine appearance rate, an index of protein breakdown, in HF patients; whereas no group difference was found in the increase in the leg phenylalanine disappearance rate, an index of protein synthesis. The diminished responses of both phenylalanine balance and appearance rate to hyperinsulinaemia–hyperaminoacidaemia were related to greater circulating IL-6 (interleukin-6) levels. Our results suggest that, following a brief period of nutritional deprivation, HF patients demonstrate an impaired muscle protein anabolic response to meal-related stimuli, due to an inability to suppress muscle proteolysis, and that this diminished protein anabolic response correlates with markers of immune activation. The inability to stimulate muscle protein anabolism following periods of nutritional deficiency may contribute to muscle wasting in HF patients.
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Research Article|
August 17 2010
Impaired muscle protein anabolic response to insulin and amino acids in heart failure patients: relationship with markers of immune activation
Michael J. Toth;
*Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, U.S.A.
Correspondence: Dr Michael J. Toth (e-mail [email protected]).
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Martin M. LeWinter;
Martin M. LeWinter
*Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, U.S.A.
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Philip A. Ades;
Philip A. Ades
*Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, U.S.A.
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Dwight E. Matthews
Dwight E. Matthews
*Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, U.S.A.
†Department of Chemistry, University of Vermont College, Burlington, VT 05405, U.S.A.
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Publisher: Portland Press Ltd
Received:
February 11 2010
Revision Received:
June 04 2010
Accepted:
June 09 2010
Accepted Manuscript online:
June 09 2010
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2010 Biochemical Society
2010
Clin Sci (Lond) (2010) 119 (11): 467–476.
Article history
Received:
February 11 2010
Revision Received:
June 04 2010
Accepted:
June 09 2010
Accepted Manuscript online:
June 09 2010
Citation
Michael J. Toth, Martin M. LeWinter, Philip A. Ades, Dwight E. Matthews; Impaired muscle protein anabolic response to insulin and amino acids in heart failure patients: relationship with markers of immune activation. Clin Sci (Lond) 1 December 2010; 119 (11): 467–476. doi: https://doi.org/10.1042/CS20100110
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