title: Impact of O-GlcNAc on cardioprotection by remote ischaemic preconditioning in non-diabetic and diabetic patients.
abstract: OBJECTIVE
  Post-translational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is cardioprotective but its role in cardioprotection by remote ischaemic preconditioning (rIPC) and the reduced efficacy of rIPC in type 2 diabetes mellitus is unknown. In this study we achieved mechanistic insight into the remote stimulus mediating and the target organ response eliciting the cardioprotective effect by rIPC in non-diabetic and diabetic myocardium and the influence of O-GlcNAcylation.
  
  
  RESULTS
  The cardioprotective capacity and the influence on myocardial O-GlcNAc levels of plasma dialysate from eight healthy volunteers and eight type 2 diabetic patients drawn before and after subjection to an rIPC stimulus were tested on human isolated atrial trabeculae subjected to ischaemia/reperfusion injury. Dialysate from healthy volunteers exposed to rIPC improved post-ischaemic haemodynamic recovery (40 ± 6 vs. 16 ± 2%; P < 0.01) and increased myocardial O-GlcNAc levels. Similar observations were made with dialysate from diabetic patients before exposure to rIPC (43 ± 3 vs. 16 ± 2%; P < 0.001) but no additional cardioprotection or further increase in O-GlcNAc levels was achieved by perfusion with dialysate after exposure to rIPC (44 ± 4 and 42 ± 5 vs. 43 ± 3%; P = 0.7). The glutamine:fructose-6-phosphate amidotransferase (GFAT) inhibitor azaserine abolished the cardioprotective effects and the increment in myocardial O-GlcNAc levels afforded by plasma from diabetic patients and healthy volunteers treated with rIPC.
  
  
  CONCLUSIONS
  rIPC and diabetes mellitus per se influence myocardial O-GlcNAc levels through circulating humoral factors. O-GlcNAc signalling participates in mediating rIPC-induced cardioprotection and maintaining a state of inherent chronic activation of cardioprotection in diabetic myocardium, restricting it from further protection by rIPC.
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, Aarhus N DK-8200, Denmark. rrebekka.vibjerg@ki.au.dk
authors.forename: Rebekka V
authors.initials: RV
authors.lastname: Jensen
authors.forename: Natasha E
authors.initials: NE
authors.lastname: Zachara
authors.forename: Per H
authors.initials: PH
authors.lastname: Nielsen
authors.forename: Hans Henrik
authors.initials: HH
authors.lastname: Kimose
authors.forename: Steen B
authors.initials: SB
authors.lastname: Kristiansen
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Bøtker
mesh_terms: D000117:Acetylglucosamine / Q000032:analysis / Q000502:physiology*; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000032:analysis; D001619:beta-N-Acetylhexosaminidases / Q000032:analysis
chemical_list: D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases; D000117:Acetylglucosamine