Endogenous lithium clearance as a probable measure of end-proximal fluid delivery in the amphibian kidneys: A study of renal water and Na+ reabsorption in the hydrated and dehydrated frog Rana temporaria

Reduced availability of nitric oxide (NO) in the vasculature is a major factor contributing to the impaired action of insulin on blood flow and, therefore, insulin resistance in obese and diabetic subjects. Available evidence shows that vascular insulin resistance plays an important role in the pathogenesis of cardiovascular disease, the leading cause of death in developed nations. Interestingly, increased concentrations of L-leucine in the plasma occur in obese humans and other animals with vascular dysfunction. Among branched-chain amino acids, L-leucine is unique in inhibiting NO synthesis from L-arginine in endothelial cells and may modulate cardiovascular homeostasis in insulin resistance. Results of recent studies indicate that L-leucine is an activator of glutamine:fructose-6-phosphate aminotransferase (GFAT), which is the first and a rate-controlling enzyme in the synthesis of glucosamine (an inhibitor of endothelial NO synthesis). Through stimulating the mammalian target of rapamycin signaling pathway and thus protein synthesis, L-leucine may enhance GFAT protein expression, thereby inhibiting NO synthesis in endothelial cells. We propose that reducing circulating levels of L-leucine or endothelial GFAT activity may provide a potentially novel strategy for preventing and/or treating cardiovascular disease in obese and diabetic subjects. Such means may include dietary supplementation with either α-ketoglutarate to enhance the catabolism of L-leucine in the small intestine and other tissues or with N-ethyl-L-glutamine to inhibit GFAT activity in endothelial cells. Preventing leucine-induced activation of GFAT by nutritional supplements or pharmaceutical drugs may contribute to improved cardiovascular function by enhancing vascular NO synthesis.

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l-Leucine and NO-mediated cardiovascular function

Yang

Meininger

et al. 2015

Amino Acids

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Lithium secretion in kidneys of amphibians and reptiles under hydrated conditions

Fleishman

Nikiforov

Saulus

et al. 1997

Comparative Biochemistry and Physiology Part A: Physiology

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Fleishman

Vasilieva

Nikiforov

2001

Journal of Evolutionary Biochemistry and Physiology

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Endogenous lithium clearance as a probable measure of end-proximal fluid delivery in the amphibian kidneys: A study of renal water and Na+ reabsorption in the hydrated and dehydrated frog Rana temporaria

Cited by 5 publications

References 12 publications

l-Leucine and NO-mediated cardiovascular function

l-Leucine and NO-mediated cardiovascular function

Lithium secretion in kidneys of amphibians and reptiles under hydrated conditions

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