title: Association of hypoglutathionemia with reduced Na+/K+ ATPase activity in type 2 diabetes and microangiopathy.
abstract: OBJECTIVE
  Although recent studies link altered cellular redox state to protein dysfunction in various disease-states, such associations are least studied in clinical diabetes. Therefore, this study assessed the levels of reduced glutathione (GSH) and Na(+)/K(+) ATPase activities in type 2 diabetic patients with and without microangiopathy.
  
  
  METHODS
  The study group comprised of a total of 160 subjects, which included non-diabetic healthy controls (n = 40) and type 2 diabetic patients without (n = 60) and with microangiopathy (n = 60), defined as presence of retinopathy with or without nephropathy. Erythrocyte Na(+)/K(+) ATPase activity and GSH levels were estimated spectrophotometrically and fluorometry was used to determine the plasma thiobarbituric acid reactive substances (TBARS) and serum advanced glycation end products (AGEs).
  
  
  RESULTS
  GSH levels in diabetic subjects without (4.8+/- 0.15 mumol/g Hb) and with microangiopathy (5.2+/- 0.14 micromol/g Hb) were significantly lower (p < 0.001) compared to control subjects (6.3 +/- 0.14 mumol/g Hb). Erythrocyte Na(+)/K(+) ATPase activity was significantly reduced (p < 0.001) in diabetes subjects with (272 +/- 7 nmol Pi/mg protein/h) and without microangiopathy (304 +/- 8) compared to control (374 +/- 6) subjects. TBARS were significantly higher (p < 0.001) in diabetes subjects with (10.65 +/- 0.81 nM/ml) and without microangiopathy (9.90 +/- 0.5 nM/ml) compared to control subjects (5.18 +/- 0.18 nM/ml). Advanced glycation end product levels were also significantly (p < 0.001) elevated in diabetic subjects with microangiopathy (8.2+/- 1.8 AU) when compared to diabetes subjects without microangiopathy (7.0 +/- 2.0 AU) and control subjects (4.6 +/- 1.9 AU). On multivariate regression analysis, GSH levels showed a positive association with the Na(+)/K(+) ATPase activity and negative association with TBARS and AGE levels.
  
  
  CONCLUSIONS
  Hypoglutathionemia and increased oxidative stress appears to be early biochemical aberrations in diabetes, and through protein alterations, oxidative stress and redox modifications may contribute to pathogenesis of diabetic microangiopathy.
authors.affiliation: Madras Diabetes Research Foundation and Dr. Mohans' M.V. Diabetes Specialities Centre, Chennai, India.
authors.forename: Rangasamy
authors.initials: R
authors.lastname: Sampathkumar
authors.forename: Muthuswamy
authors.initials: M
authors.lastname: Balasubramanyam
authors.forename: Cherian
authors.initials: C
authors.lastname: Tara
authors.forename: Mohan
authors.initials: M
authors.lastname: Rema
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000201:enzymology / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000150:complications / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000150:complications / Q000378:metabolism*; D004912:Erythrocytes / Q000201:enzymology; D005978:Glutathione / Q000097:blood; D017127:Glycation End Products, Advanced / Q000097:blood; D006801:Humans; D015227:Lipid Peroxidation; D008875:Middle Aged; D018384:Oxidative Stress; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D017392:Thiobarbituric Acid Reactive Substances; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione