Abstract
Oxidative stress plays a leading role in the progression of diabetic secondary complications, e. g., of cardio-vascular illnesses. Physical activity has been shown to delay and even prevent the progression of type 2 diabetes by improving the antioxidative capacity and thereby decreasing systemic oxidative stress. Peroxiredoxins (PRDX) are important antioxidative components that are highly abundant in erythrocytes. The present study examines the influence of glycemic control and physical fitness on oxidative stress and the peroxiredoxin system in the erythrocytes of non-insulin-dependent type 2 diabetic men (n =22, years=61±10) at rest. Oxidative stress was measured by immunohistochemical stainings for 8-iso-prostaglandin-F2α (8-Iso-PGF) and the overoxidized form of peroxiredoxins (PRDX-SO2–3 ). Peroxiredoxin isoforms PRDX1 and PRDX2 were also quantified immunohistochemically. Physical fitness was determined during the WHO-step test. Regression analyses showed a positive relationship between 8-Iso-PGF plotted against HbA1c (hyperbolic curve (y=a+b/x), R2 =0.346, P =0.013), a positive relationship between 8-Iso-PGF plotted against fasting glucose (hyperbolic curve (y=a+b/x), R2 =0.440, P =0.003), as well as positive relationships between PRDX2 plotted against VO2peak (S-curve (y=ea+b/x ), R2 =0.259, P =0.018) and between PRDX2 plotted against the workload corresponding to the 4 mmol/l blood lactate concentration (hyperbolic curve (y=a+b/x), R2 =0.203, P =0.041). Further significant relationships were not found.
Conclusions: Poor glycemic control may increase oxidative stress in the erythrocytes of type 2 diabetic men. Good physical fitness seems to be associated with increased peroxiredoxin contents. Therefore, it can be speculated that physical training can contribute to the improvement of the erythrocyte peroxiredoxin system to counteract free radicals in type 2 diabetic patients.
Key words
diabetes - oxidative stress - obesity - cardiovascular incidences
References
1
Alexander RW.
Hypertension and the pathogenesis of atherosclerosis. Oxidative stress and the mediation of arterial inflammatory response: a new perspective.
Hypertension.
1995;
25
155-161
2
Arai K, Iizuka S, Tada Y. et al .
Increase in glycosylated form of erythrocyte Cu-Zn-superoxide dismutase in diabetes and close association of the nonenzymatic glycosylation with the enzyme activity.
Biochim Biophys Acta.
1987;
924
292-296
3
Araujo FB, Barbosa DS, Hsin CY. et al .
Evaluation of oxidative stress in patients with hyperlipidemia.
Atherosclerosis.
1995;
117
61-71
4
Ashton T, Rowlands CC, Jones E. et al .
Electron spin resonance spectrometric detection of oxygen-centred radicals in human serum following exhaustive exercise.
Eur J Appl Physiol Occup Physiol.
1998;
77
498-502
5
Atalay M, Laaksonen DE.
Diabetes, oxidative stress and physical exercise.
J Sports Sci Med.
2002;
1
1-14
6
Brownlee M.
Biochemistry and molecular cell biology of diabetic complications.
Nature.
2001;
414
813-820
7
Ceriello A, Mercuri F, Quagliaro L. et al .
Detection of nitrotyrosine in the diabetic plasma: evidence of oxidative stress.
Diabetologia.
2001;
44
834-838
8
Cho CS, Lee S, Lee GT. et al .
Irreversible inactivation of glutathione peroxidase 1 and reversible inactivation of peroxiredoxin II by H2O2 in red blood cells.
Antioxid Redox Signal.
2010;
12
1235-1246
9
Clodi M, Resl M, Stelzeneder D. et al .
Interactions of glucose metabolism and chronic heart failure.
Exp Clin Endocrinol Diabetes.
2009;
117
99-106
10
Cosentino F, Hishikawa K, Katusic ZS. et al .
High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells.
Circulation..
1997;
1
25-28
11
Goodarzi MT, Varmaziar L, Navidi AA. et al .
Study of oxidative stress in type 2 diabetic patients and its relationship with glycated hemoglobin.
Saudi Med J.
2008;
29
503-506
12
Iborra RT, Ribeiro IC, Neves MQ. et al .
Aerobic exercise training improves the role of high-density lipoprotein antioxidant and reduces plasma lipid peroxidation in type 2 diabetes mellitus.
Scand J Med Sci Sports.
2008;
18
742-750
13
Ide T, Tsutsui H, Ohashi N. et al .
Greater oxidative stress in healthy young men compared with premenopausal women.
Arterioscler Thromb Vasc Biol.
2002;
22
438-442
14
Inoguchi T, Li P, Umeda F. et al .
High glucose level and free fatty acid stimulate reactive oxygen protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells.
Diabetes.
2000;
49
1939-1945
15
Julius U, Drel VR, Grässler J. et al .
Nitrosylated proteins in monocytes as a new marker of oxidative-nitrosative stress in diabetic subjects with macroangiopathy.
Exp Clin Endocrinol Diabetes.
2009;
117
72-77
16
Kaneto H, Katakami N, Matsuhisa M. et al .
Role of reactive oxygen species in the progression of type 2 diabetes and atherosclerosis.
Mediators Inflamm.
2010;
2010
453892
17
Kotake M, Shinohara R, Kato K. et al .
Reduction of activity, but no decrease in concentration, of erythrocyte Cu,Zn-superoxide dismutase by hyperglycaemia in diabetic patients.
Diabet Med.
1998;
5
668-671
18
Laaksonen DE, Atalay M, Niskanen L. et al .
Increased resting and exercise-induced oxidative stress in young IDDM men.
Diabetes Care.
1996;
19
569-574
19
Low FM, Hampton MB, Winterbourn CC.
Peroxiredoxin 2 and peroxide metabolism in the erythrocyte.
Antioxid Redox Signal.
2008;
10
1621-1630
20
Maritim AC, Sanders RA, Watkins JB.
Diabetes, oxidative stress, and antioxidants: A review.
J Biochem Mol Toxicol.
2003;
17
24-38
21
Maxwell SR, Thomason H, Sandler D. et al .
Poor glycaemic control is associated with reduced serum free radical scavenging (antioxidant) activity in non-insulin-dependent diabetes mellitus.
Ann Clin Biochem.
1997;
34
628-644
22
Minetti M, Agati L, Malorni W.
The microenvironment can shift erythrocytes from a friendly to a harmful behavior: pathogenetic implications for vascular diseases.
Cardiovasc Res.
2007;
75
21-28
23
Misra HP, Fridovich I.
The generation of superoxide radical during the autoxidation of hemoglobin.
J Biol Chem.
1972;
247
6960-6962
24
Miyazaki H, Oh-ishi S, Ookawara T. et al .
Strenuous endurance training in humans reduces oxidative stress following exhaustive exercise.
Eur J Appl Physiol.
2001;
84
1-6
25
Ohno H, Yahata T, Sato Y. et al .
Physical training and fasting erythrocyte activities of free radical scavenging enzyme systems in sedentary men.
Eur J Appl Physiol Occup Physiol.
1988;
57
173-176
26
Osuntokl AA, Fasanmade OA, Adekola AO. et al .
Lipid peroxidation and erythrocyte fragility in poorly controlled type 2 diabetes mellitus.
Nig Q J Hosp Med.
2007;
17
148-151
27
Ouslimani N, Peynet J, Bonnefont-Rousselot D. et al .
Metformin decreases intracellular production of reactive oxygen species in aortic endothelial cells.
Metabolism.
2005;
54
829-834
28
Pandey KB, Mishra N, Rizvi SI.
Protein oxidation biomarkers in plasma of type 2 diabetic patients.
Clin Biochem.
2010;
43
508-511
29
Roberts CK, Vaziri ND, Barnard RJ.
Effect of diet and exercise intervention on blood pressure, insulin, oxidative stress, and nitric oxide availability.
Circulation.
2002;
106
2530-2532
30
Schmitt S, Linder M, Ständker L. et al .
Identification of CML-modified proteins in hemofiltrate of diabetic patients by proteome analysis.
Exp Clin Endocrinol Diabetes.
2008;
116
26-34
31
Suhr F, Porten S, Hertrich T. et al .
Intensive exercise induces changes of endothelial nitric oxide synthase pattern in human erythrocytes.
Nitric Oxide.
2009;
20
95-103
32
Venditti P, Di Meo S.
Antioxidants, tissue damage, and endurance in trained and untrained young male rats.
Arch Biochem Biophys.
1996;
331
63-68
33
Winterbourn CC, Stern A.
Human red cells scavenge extracellular hydrogen peroxide and inhibit formation of hypochlorous acid and hydroxyl radical.
J Clin Invest.
1987;
80
1486-1491
34
Wolff SP, Dean RT.
Glucose autoxidation and protein modification.
Biochem J.
1987;
245
243-250
Correspondence
C. Brinkmann
Department of Molecular and
Cellular Sport Medicine
German Sport University
Cologne
Am Sportpark Müngersdorf 6
50933 Cologne
Germany
Telefon: +49/221/4982 54 40
Fax: +49/221/4982 83 70
eMail: ch.brinkmann@gmx.net