Effects of l-arginine supplementation on blood flow, oxidative stress status and exercise responses in young adults with uncomplicated type I diabetes
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Background and aims
Vascular disease is the principal cause of death and disability in patients with diabetes, and endothelial dysfunction seems to be the major cause in its pathogenesis. Since l-arginine levels are diminished in conditions such as type 1 and type 2 diabetes, in this work we aimed to verify the effects of l-arginine supplementation (7 g/day) over the endothelial function and oxidative stress markers in young male adults with uncomplicated type 1 diabetes. We also investigated the influences of l-arginine administration on vascular/oxidative stress responses to an acute bout of exercise.
Ten young adult male subjects with uncomplicated type 1 diabetes and twenty matched controls volunteered for this study. We analysed the influence of l-arginine supplementation (7 g/day during 1 week) over lower limb blood flow (using a venous occlusion plethysmography technique), oxidative stress marker (TBARS, Carbonyls), anti-oxidant parameters (uric acid and TRAP) and total tNOx in rest conditions and after a single bout of submaximal exercise (VO2 at 10 % below the second ventilatory threshold). Data described as mean ± standard error (SE). Alpha level was P < 0.05.
Glycaemic control parameters were altered in type 1 diabetic subjects, such as HbA1c (5.5 ± 0.03 vs. 8.3 ± 0.4 %) and fasted glycaemia (94.8 ± 1.4 vs. 183 ± 19 mg/dL). Oxidative stress/damage markers (carbonyls and TBARS) were increased in the diabetic group, while uric acid was decreased. Rest lower limb blood flow was lower in type 1 diabetic subjects than in healthy controls (3.53 ± 0.35 vs. 2.66 ± 0.3 ml 100 ml−¹ min−¹). l-Arginine supplementation completely recovered basal blood flow to normal levels in type 1 diabetics’ subjects (2.66 ± 0.3 to 4.74 ± 0.86 ml 100 ml−¹ min−¹) but did not interfere in any parameter of redox state or exercise.
Our findings highlight the importance of l-arginine for the improvement of vascular function in subjects with diabetes, indicating that l-arginine supplementation could be an essential tool for the treatment for the disease complications, at least in non-complicated diabetes. However, based on our data, it is not possible to draw conclusions regarding the mechanisms by which l-arginine therapy is inducing improvements on cardiovascular function, but this important issue requires further investigations.
Keywordsl-Arginine Type 1 diabetes Blood flow Oxidative stress
This work was supported by the National Council for Scientific and Technological Development (CNPq, Brazil).
Conflict of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
- 2.Huysman E, Mathieu C (2009) Diabetes and peripheral vascular disease. Acta Chir Belg 109:587–594Google Scholar
- 4.Poston L, Taylor PD (1995) Glaxo/MRS young investigator prize. Endothelium-mediated vascular function in insulin-dependent diabetes mellitus. Clin Sci (Lond) 88:245–255Google Scholar
- 6.Newsholme P, Homem De Bittencourt PI, C OH, De Vito G, Murphy C, Krause MS (2009) Exercise and possible molecular mechanisms of protection from vascular disease and diabetes: the central role of ROS and nitric oxide. Clin Sci (Lond) 118:341–349Google Scholar
- 12.Fu WJ, Haynes TE, Kohli R, Hu J, Shi W, Spencer TE, Carroll RJ, Meininger CJ, Wu G (2005) Dietary l-arginine supplementation reduces fat mass in Zucker diabetic fatty rats. J Nutr 135:714–721Google Scholar
- 17.Wu G, Collins JK, Perkins-Veazie P, Siddiq M, Dolan KD, Kelly KA, Heaps CL, Meininger CJ (2007) Dietary supplementation with watermelon pomace juice enhances arginine availability and ameliorates the metabolic syndrome in Zucker diabetic fatty rats. J Nutr 137:2680–2685Google Scholar
- 18.Lucotti P, Monti L, Setola E, La Canna G, Castiglioni A, Rossodivita A, Pala MG, Formica F, Paolini G, Catapano AL, Bosi E, Alfieri O, Piatti P (2009) Oral l-arginine supplementation improves endothelial function and ameliorates insulin sensitivity and inflammation in cardiopathic nondiabetic patients after an aortocoronary bypass. Metabolism 58:1270–1276CrossRefGoogle Scholar
- 20.Martina V, Masha A, Gigliardi VR, Brocato L, Manzato E, Berchio A, Massarenti P, Settanni F, Della Casa L, Bergamini S, Iannone A (2008) Long-term N-acetylcysteine and l-arginine administration reduces endothelial activation and systolic blood pressure in hypertensive patients with type 2 diabetes. Diabetes Care 31:940–944CrossRefGoogle Scholar
- 21.Lucotti P, Setola E, Monti LD, Galluccio E, Costa S, Sandoli EP, Fermo I, Rabaiotti G, Gatti R, Piatti P (2006) Beneficial effects of a long-term oral l-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients. Am J Physiol Endocrinol Metab 291:E906–E912CrossRefGoogle Scholar
- 22.Natarajan Sulochana K, Lakshmi S, Punitham R, Arokiasamy T, Sukumar B, Ramakrishnan S (2002) Effect of oral supplementation of free amino acids in type 2 diabetic patients—a pilot clinical trial. Med Sci Monit 8:CR131–137Google Scholar
- 26.Palloshi A, Fragasso G, Piatti P, Monti LD, Setola E, Valsecchi G, Galluccio E, Chierchia SL, Margonato A (2004) Effect of oral l-arginine on blood pressure and symptoms and endothelial function in patients with systemic hypertension, positive exercise tests, and normal coronary arteries. Am J Cardiol 93:933–935CrossRefGoogle Scholar
- 31.Pollack ML, Schmidt DH, Jackson AS (1980) Measurement of cardio-respiratory fitness and body composition in the clinical setting. Compr Ther 6:12–27Google Scholar
- 33.Duncan GE, Howley ET, Johnson BN (1997) Applicability of VO2max criteria: discontinuous versus continuous protocols. Med Sci Sports Exerc 29:273–278Google Scholar
- 37.Copeland SR, Mills MC, Lerner JL, Crizer MF, Thompson CW, Sullivan JM (1996) Hemodynamic effects of aerobic vs resistance exercise. J Hum Hypertens 10:747–753Google Scholar
- 39.Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
- 47.Wu G, Meininger CJ (2000) Arginine nutrition and cardiovascular function. J Nutr 130:2626–2629Google Scholar
- 49.Kilbom A, Wennmalm A (1976) Endogenous prostaglandins as local regulators of blood flow in man: effect of indomethacin on reactive and functional hyperaemia. J Physiol 257:109–121Google Scholar