Molecular and Cellular Biochemistry

, Volume 282, Issue 1–2, pp 169–176

Association of hypoglutathionemia with reduced Na+/K+ ATPase activity in type 2 diabetes and microangiopathy

  • Rangasamy Sampathkumar
  • Muthuswamy Balasubramanyam
  • Cherian Tara
  • Mohan Rema
  • Viswanathan Mohan


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 μmol/g Hb) and with microangiopathy (5.2± 0.14 μmol/g Hb) were significantly lower (p < 0.001) compared to control subjects (6.3± 0.14 μmol/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. Conclusion: 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.

Key words

advanced glycation end products (AGEs) diabetes Na+/K+ ATPase oxidative stress reduced glutathione 


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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Rangasamy Sampathkumar
    • 1
  • Muthuswamy Balasubramanyam
    • 1
    • 2
  • Cherian Tara
    • 1
  • Mohan Rema
    • 1
  • Viswanathan Mohan
    • 1
  1. 1.Madras Diabetes Research Foundation and Dr. Mohans' M.V. Diabetes Specialities CentreChennaiIndia
  2. 2.Department of Cell and Molecular BiologyMadras Diabetes Research FoundationChennaiIndia

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