title: Muscle histidine-containing dipeptides are elevated by glucose intolerance in both rodents and men.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Movement and Sport Sciences, Ghent University, Ghent, Belgium.
authors: Sanne
authors: S
authors: Stegen
authors: Department of Movement and Sport Sciences, Ghent University, Ghent, Belgium.
authors: Inge
authors: I
authors: Everaert
authors: Department of Kinesiology, Exercise Physiology Research Centre, KU Leuven, Heverlee, Belgium.
authors: Louise
authors: L
authors: Deldicque
authors: Department of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
authors: Silvia
authors: S
authors: Vallova
authors: Monash Centre for Health, Research and Implementation, Faculty of Medicine, Nursing & Health Sciences, Melbourne, Australia.
authors: Barbora
authors: B
authors: de Courten
authors: Department of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia; Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors: Barbara
authors: B
authors: Ukropcova
authors: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors: Jozef
authors: J
authors: Ukropec
authors: Department of Movement and Sport Sciences, Ghent University, Ghent, Belgium.
authors: Wim
authors: W
authors: Derave
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D004151:Dipeptides / Q000737:chemistry* / Q000378:metabolism*; D005260:Female; D018149:Glucose Intolerance / Q000378:metabolism* / Q000503:physiopathology; D005951:Glucose Tolerance Test; D006639:Histidine; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009043:Motor Activity; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats
chemical_list: D015415:Biomarkers; D004151:Dipeptides; D006639:Histidine