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Administration of glutathione in patients with type 2 diabetes mellitus increases the platelet constitutive nitric oxide synthase activity and reduces PAI-1.

Abstract
Several studies suggest that nitric oxide (NO) production is impaired in diabetes mellitus. Reduced levels of NO could contribute to cardiovascular mortality. Furthermore, NO synthesis is impaired in glutathione (GSH)-depleted human umbilical vein endothelial cells and GSH is reduced in patients with type 2 diabetes mellitus (T2DM). We tested the hypothesis that treatment with GSH may improve platelet constitutive NO sinthase (cNOS) activity in patients with T2DM. Fifteen patients with T2DM underwent a treatment with GSH 600 mg/day i.m. for 10 days. With respect to the basal values on the 10th day of treatment, the red blood cell GSH concentration and platelets cNOS increased (1.4+/-0.1 vs 1.9+/-0.1 micromol/10(10) RBC, p<0.001 and 0.7+/-0.1 vs 2.9+/-0.2 fmol x min(-1) x 10(-9) PLTs, p<0.001, respectively) and the plasma PAI-1 levels diminished (81.4+/-3.7 vs 68.7+/-4.0 ng/ml, p<0.002). A negative correlation between the cNOS and the PAI-1 was found on the basal values. After a wash-out of 30 days the values of red blood cell GSH concentration, platelet cNOS activity and PAI-1 Ag returned to the basal levels. These data suggest that the administration of GSH, in patients with T2DM, is able to improve platelet cNOS activity together with a reduction of PAI-1.
AuthorsV Martina, G A Bruno, E Zumpano, C Origlia, L Quaranta, G P Pescarmona
JournalJournal of endocrinological investigation (J Endocrinol Invest) Vol. 24 Issue 1 Pg. 37-41 (Jan 2001) ISSN: 0391-4097 [Print] Italy
PMID11227730 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Plasminogen Activator Inhibitor 1
  • Nitric Oxide
  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Glutathione
Topics
  • Aged
  • Blood Platelets (enzymology)
  • Diabetes Mellitus, Type 2 (blood, drug therapy)
  • Endothelium, Vascular (metabolism)
  • Erythrocytes (metabolism)
  • Female
  • Glutathione (administration & dosage, blood, therapeutic use)
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide (biosynthesis)
  • Nitric Oxide Synthase (blood)
  • Nitric Oxide Synthase Type III
  • Plasminogen Activator Inhibitor 1 (blood)
  • Umbilical Veins

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