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Muscle histidine-containing dipeptides are elevated by glucose intolerance in both rodents and men

(2015) PLOS ONE. 10(3).
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Abstract
Objective : Muscle carnosine and its methylated form anserine are histidine-containing dipeptides. Both dipeptides have the ability to quench reactive carbonyl species and previous studies have shown that endogenous tissue levels are decreased in chronic diseases, such as diabetes. Design and Methods : Rodent study: Skeletal muscles of rats and mice were collected from 4 different diet-intervention studies, aiming to induce various degrees of glucose intolerance: 45% high-fat feeding (male rats), 60% high-fat feeding (male rats), cafeteria feeding (male rats), 70% high-fat feeding (female mice). Body weight, glucose-tolerance and muscle histidine-containing dipeptides were assessed. Human study: Muscle biopsies were taken from m. vastus lateralis in 35 males (9 lean, 8 obese, 9 prediabetic and 9 newly diagnosed type 2 diabetic patients) and muscle carnosine and gene expression of muscle fiber type markers were measured. Results : Diet interventions in rodents (cafeteria and 70% high-fat feeding) induced increases in body weight, glucose intolerance and levels of histidine-containing dipeptides in muscle. In humans, obese, prediabetic and diabetic men had increased muscle carnosine content compared to the lean (+21% (p>0.1), +30% (p<0.05) and +39% (p<0.05), respectively). The gene expression of fast-oxidative type 2A myosin heavy chain was increased in the prediabetic (1.8-fold, p<0.05) and tended to increase in the diabetic men (1.6-fold, p = 0.07), compared to healthy lean subjects. Conclusion : Muscle histidine-containing dipeptides increases with progressive glucose intolerance, in male individuals (cross-sectional). In addition, high-fat diet-induced glucose intolerance was associated with increased muscle histidine-containing dipeptides in female mice (interventional). Increased muscle carnosine content might reflect fiber type composition and/or act as a compensatory mechanism aimed at preventing cell damage in states of impaired glucose tolerance.
Keywords
METABOLISM, HUMAN SKELETAL-MUSCLE, MICE, EXERCISE, SUPPLEMENTATION, IN-VIVO, GENE-EXPRESSION, CARNOSINE CONTENT, HUMAN VASTUS LATERALIS, BETA-ALANINE

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Chicago
Stegen, Sanne, Inge Everaert, Louise Deldicque, Silvia Vallova, Barbora de Courten, Barbara Ukropcova, Jozef Ukropec, and Wim Derave. 2015. “Muscle Histidine-containing Dipeptides Are Elevated by Glucose Intolerance in Both Rodents and Men.” Plos One 10 (3).
APA
Stegen, S., Everaert, I., Deldicque, L., Vallova, S., de Courten, B., Ukropcova, B., Ukropec, J., et al. (2015). Muscle histidine-containing dipeptides are elevated by glucose intolerance in both rodents and men. PLOS ONE, 10(3).
Vancouver
1.
Stegen S, Everaert I, Deldicque L, Vallova S, de Courten B, Ukropcova B, et al. Muscle histidine-containing dipeptides are elevated by glucose intolerance in both rodents and men. PLOS ONE. 2015;10(3).
MLA
Stegen, Sanne, Inge Everaert, Louise Deldicque, et al. “Muscle Histidine-containing Dipeptides Are Elevated by Glucose Intolerance in Both Rodents and Men.” PLOS ONE 10.3 (2015): n. pag. Print.
@article{6867213,
  abstract     = {Objective : Muscle carnosine and its methylated form anserine are histidine-containing dipeptides. Both dipeptides have the ability to quench reactive carbonyl species and previous studies have shown that endogenous tissue levels are decreased in chronic diseases, such as diabetes. 
Design and Methods : Rodent study: Skeletal muscles of rats and mice were collected from 4 different diet-intervention studies, aiming to induce various degrees of glucose intolerance: 45\% high-fat feeding (male rats), 60\% high-fat feeding (male rats), cafeteria feeding (male rats), 70\% high-fat feeding (female mice). Body weight, glucose-tolerance and muscle histidine-containing dipeptides were assessed. Human study: Muscle biopsies were taken from m. vastus lateralis in 35 males (9 lean, 8 obese, 9 prediabetic and 9 newly diagnosed type 2 diabetic patients) and muscle carnosine and gene expression of muscle fiber type markers were measured. 
Results : Diet interventions in rodents (cafeteria and 70\% high-fat feeding) induced increases in body weight, glucose intolerance and levels of histidine-containing dipeptides in muscle. In humans, obese, prediabetic and diabetic men had increased muscle carnosine content compared to the lean (+21\% (p{\textrangle}0.1), +30\% (p{\textlangle}0.05) and +39\% (p{\textlangle}0.05), respectively). The gene expression of fast-oxidative type 2A myosin heavy chain was increased in the prediabetic (1.8-fold, p{\textlangle}0.05) and tended to increase in the diabetic men (1.6-fold, p = 0.07), compared to healthy lean subjects. 
Conclusion : Muscle histidine-containing dipeptides increases with progressive glucose intolerance, in male individuals (cross-sectional). In addition, high-fat diet-induced glucose intolerance was associated with increased muscle histidine-containing dipeptides in female mice (interventional). Increased muscle carnosine content might reflect fiber type composition and/or act as a compensatory mechanism aimed at preventing cell damage in states of impaired glucose tolerance.},
  articleno    = {e0121062},
  author       = {Stegen, Sanne and Everaert, Inge and Deldicque, Louise and Vallova, Silvia and de Courten, Barbora and Ukropcova, Barbara and Ukropec, Jozef and Derave, Wim},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keyword      = {METABOLISM,HUMAN SKELETAL-MUSCLE,MICE,EXERCISE,SUPPLEMENTATION,IN-VIVO,GENE-EXPRESSION,CARNOSINE CONTENT,HUMAN VASTUS LATERALIS,BETA-ALANINE},
  language     = {eng},
  number       = {3},
  pages        = {13},
  title        = {Muscle histidine-containing dipeptides are elevated by glucose intolerance in both rodents and men},
  url          = {http://dx.doi.org/10.1371/journal.pone.0121062},
  volume       = {10},
  year         = {2015},
}

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