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Diabetic rats exhibit decrease in plasma arginine , NO synthesis and tetrahydrobiopterin in endothelial cells (EC ) . Treatment with L -arginine may be beneficial for enhancing NO synthesis in diseases associated with endothelial dysfunction . However , little is known about the mechanism responsible for the stimulatory effect of arginine on endothelial NO synthesis . We hypothesized that dietary arginine supplementation increases BH4 for NO synthesis in EC of diabetic rats , thereby preventing endothelial dysfunction . In experiment I , streptozotocin (STZ ) induced -diabetic male Sprague Dawley (SD ) rats (a model of type -I diabetes ) were individually pair -fed a casein -based diet on the basis of feed intake (per kg body weight ) of non -diabetic SD rats . Addition of arginine -HCl or alanine to drinking water for the rats were adjusted daily to ensure isonitrogenous provision per kg body weight . In non -diabetic rats , arginine supplementation increased plasma arginine (144 % ) , plasma insulin (44 % ) , EC arginine (88 % ) , EC BH4 (106 % ) and EC NO synthesis (80 % ) , compared with alanine treatment . In diabetic rats , arginine supplementation reduced body weight loss (36 % ) , and plasma glucose (54 % ) , and increased plasma arginine (110 % ) , plasma insulin (209 % ) , EC arginine (173 % ) , EC BH4 (128 % ) and EC NO synthesis (125 % ) , compared with alanine treatment . In experiment II , male Zucker diabetic fatty (ZDF ) rats (a model of type -II diabetes ) were individually pair -fed a Purina 5008 diet on the basis of feed intake by alanine -treated diabetic rats (per kg body wt ) . Addition of arginine -HCl or alanine to drinking water for the rats was adjusted daily to ensure isonitrogenous provision per kg body weight . Arginine supplementation to ZDF rats did not affect plasma glucose and insulin , reduced epidididmal fat (30 % ) , abdominal fat (43 % ) and body weight gain (18 % ) , and increased plasma arginine (273 % ) , EC arginine (197 % ) , EC BH4 (120 % ) and EC NO synthesis (122 % ) , compared with alanine -treated ZDF rats . These results show that dietary L -arginine supplementation increases BH4 and NO synthesis in EC of both STZ -diabetic and ZDF rats . Strikingly , arginine treatment prevented hyperglycemia in STZ -diabetic SD rats and reduced obesity in ZDF rats . Collectively , results demonstrate that oral administration of arginine is beneficial for both type -I and type -II diabetic rats . |
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