title: Reversal of hyperglycemia: effects on nitric oxide signaling.
abstract: BACKGROUND
  Hyperglycemia in patients with acute coronary syndromes is associated with poor outcomes, and its rapid correction with insulin infusion has been shown to restore platelet responsiveness to nitric oxide and to suppress superoxide (O2(-)) generation. Thioredoxin-interacting protein has emerged recently as a pivotal modulator of hyperglycemia-induced inflammation, O2(-) production, and impairment of nitric oxide signaling, but it is not known whether its expression in platelets can be downregulated rapidly.
  
  
  METHODS
  In 12 hyperglycemic patients with acute coronary syndrome, we evaluated the putative role of thioredoxin-interacting protein suppression in the platelet nitric oxide response after reversal of hyperglycemia with insulin infusion.
  
  
  RESULTS
  Insulin infusion for 13.0 ± 0.8 (standard error of the mean) hours decreased blood glucose level from 16.6 ± 1.6 mmol/L to 8.7 ± 1.4 mmol/L (P = .002). This induced (1) sensitization of antiaggregatory response to nitric oxide (from 6.5% ± 7.7% to 39.7% ± 7.0%, P < .0001); (2) improved endothelial progenitor cell function (from a median of 45 to 180 colony-forming units, P < .05); and (3) decreases of whole blood reactive oxygen species content (P < .05). However, there was no significant suppression of platelet thioredoxin-interacting protein expression (mean decrease, 59 arbitrary units; 95% confidence interval, -193 to +74).
  
  
  CONCLUSIONS
  Correction of hyperglycemia in patients with acute coronary syndrome rapidly reverses oxidative stress, restoring both platelet nitric oxide responsiveness and endothelial progenitor cell function, but this process is largely or entirely independent of thioredoxin-interacting protein.
authors.affiliation: Cardiology and Clinical Pharmacology Department, Basil Hetzel Institute, the Queen Elizabeth Hospital, Woodville, South Australia, Australia; University of Adelaide, Adelaide, Australia.
authors.forename: Cher-Rin
authors.initials: CR
authors.lastname: Chong
authors.affiliation: Cardiology and Clinical Pharmacology Department, Basil Hetzel Institute, the Queen Elizabeth Hospital, Woodville, South Australia, Australia; University of Adelaide, Adelaide, Australia.
authors.forename: Saifei
authors.initials: S
authors.lastname: Liu
authors.affiliation: Cardiology and Clinical Pharmacology Department, Basil Hetzel Institute, the Queen Elizabeth Hospital, Woodville, South Australia, Australia; University of Adelaide, Adelaide, Australia.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Licari
authors.affiliation: Cardiology and Clinical Pharmacology Department, Basil Hetzel Institute, the Queen Elizabeth Hospital, Woodville, South Australia, Australia.
authors.forename: Tamila
authors.initials: T
authors.lastname: Heresztyn
authors.affiliation: Cardiology and Clinical Pharmacology Department, Basil Hetzel Institute, the Queen Elizabeth Hospital, Woodville, South Australia, Australia; University of Adelaide, Adelaide, Australia.
authors.forename: Yuliy Y
authors.initials: YY
authors.lastname: Chirkov
authors.affiliation: Cardiology and Clinical Pharmacology Department, Basil Hetzel Institute, the Queen Elizabeth Hospital, Woodville, South Australia, Australia; University of Adelaide, Adelaide, Australia.
authors.forename: Doan T
authors.initials: DT
authors.lastname: Ngo
authors.affiliation: Cardiology and Clinical Pharmacology Department, Basil Hetzel Institute, the Queen Elizabeth Hospital, Woodville, South Australia, Australia; University of Adelaide, Adelaide, Australia. Electronic address: john.horowitz@adelaide.edu.au.
authors.forename: John D
authors.initials: JD
authors.lastname: Horowitz
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D003402:Creatine Kinase / Q000097:blood; D015536:Down-Regulation; D066026:Endothelial Progenitor Cells / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D020107:Troponin T / Q000097:blood
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D003402:Creatine Kinase; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D009569:Nitric Oxide; D017382:Reactive Oxygen Species; D020107:Troponin T; C486715:TXNIP protein, human; C517652:hemoglobin A1c protein, human
keywords: Acute coronary syndrome; Endothelial progenitor cell; Hyperglycemia; Nitric oxide; Oxidative stress; Thioredoxin-interacting protein