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

Sampathkumar, R and Balasubramanyam, M and Tara, C and Rema, M and Mohan, V (2006) Association of hypoglutathionemia with reduced Na+/K+ ATPase activity in type 2 diabetes and microangiopathy. Molecular and Cellular Biochemistry, 282 (1-2). pp. 169-76. ISSN 0300-8177

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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. 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.

Item Type:Article
Official URL/DOI:
Uncontrolled Keywords:advanced glycation end products (AGEs); diabetes, Na+/K+ ATPase; oxidative stress; reduced glutathione
Subjects:Diabetes > CURES
Biochemistry,Cell and Molecular Signalling > Molecular Biology-Diabetes
Divisions:Department of Cell and Molecular Biology
Department of Diabetology
ID Code:112
Deposited On:24 Oct 2009 15:05
Last Modified:24 Oct 2009 15:05

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