Abstract
L-arginine is a nutritionally important amino acid that controls a wide spectrum of cellular functions and physiological processes, acting by itself or through its various metabolites. There are several factors that determine overall L-arginine homeostasis: dietary supplementation, endogenous de novo synthesis, whole-body protein turnover and its extensive metabolism. The destiny of L-arginine is determined by the complex network of enzymes and pathways differentially expressed according to health and disease status. Diabetes is characterized by reduced concentrations of L-arginine in plasma and many tissues, and failure of its metabolic effects. Emerging data suggest that oral supplementation of L-arginine exerts multiple beneficial effects on the complex etiological and pathophysiological basis of diabetes including: i) β-cell function and mass and ii) obesity and peripheral insulin resistance. This review emphasizes important aspects of L-arginine action which classifies this amino acid as a promising therapeutic approach in the treatment of diabetes.
Highlights
Research into L-arginine has a rich history, and started with its isolation from lupin seedlings in 1886 [1], through the clarification of its metabolic pathways as well as nutritional needs, to the discovery that this amino acid is a precursor for nitric oxide (NO) [2], and the recognition of NO as an endothelium-derived relaxing factor [3, 4]
Roy et al [159] showed that infusion of the NO synthases (NOSs) inhibitor, NGmonomethyl-L-arginine (L-NMMA), in rats inhibited insulin-mediated glucose uptake in muscles and various adipose tissue depots, while Marliss et al [160] reported that the increase in plasma level of this NOS inhibitor correlates with insulin resistance in obese and aging subjects
The understanding that diabetes is a chronic multifactorial disease, which is poorly treated with the available therapeutic approaches, has stimulated a renewed interest in the development of novel safe and effective therapies for this disease
Summary
Research into L-arginine has a rich history, and started with its isolation from lupin seedlings in 1886 [1], through the clarification of its metabolic pathways as well as nutritional needs, to the discovery that this amino acid is a precursor for nitric oxide (NO) [2], and the recognition of NO as an endothelium-derived relaxing factor [3, 4]. Disturbances in protein and Larginine metabolism [11] result in reduced concentrations of L-arginine in plasma and in many tissues [12]. Such changes in L-arginine homeostasis can be improved by L-arginine supplementation which has been shown to increase plasma urea and protein [13] as well as arginine levels [14] in diabetes. Important progress in L-arginine research suggests that this amino acid and its metabolites play a more complex role in the regulation of whole-body energy homeostasis, and dietary supplementation of Larginine could have multiple beneficial effects in the treatment of this disease. Nutritional L-Arginine in Diabetes this review is to highlight the effects of L-arginine on: (1) -cells function and population in relation to their role in the etiology and progression of diabetes type 1 and type 2 and (2) peripheral insulin sensitivity in terms of insulin resistance and type 2 diabetes-associated obesity
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