Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced  Arginase Activity

Wijnands, Karolina A. P.; Meesters, Dennis M.; Barneveld, Kevin W. Y. van; Visschers, Ruben G.J.; Briedé, Jacob J.; Vandendriessche, Benjamin; Eijk, Hans M.H. van; Bessems, Babs A.F.M.; Hoven, Nadine van den; Wintersdorff, Christian J. H. von; Brouckaert, Peter; Bouvy, Nicole D.; Lamers, Wouter H.; Cauwels, Anje; Poeze, Martijn

doi:10.3390/nu7075217

Cited by 42 publications

(39 citation statements)

References 60 publications

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“…In total, 55 Ϯ 2% and 53 Ϯ 2% of the ingested protein became available in the circulation during the 5-h postprandial period in the PRO and PRONO3 groups, respectively. Despite previous reports that dietary strategies augmenting NO metabolism may alter gut and organ tissue perfusion (47,56), the greater plasma NO 2 Ϫ availability in the PRONO3 group did not modulate dietary protein digestion, amino acid absorption, or the amount of protein-derived amino acids that became available within the circulation after the ingestion of 20 g of protein in these older, type 2 diabetes patients.…”

Section: E330 Dietary Nitrate Co-ingestion and Muscle Protein Synthesiscontrasting

confidence: 82%

Sodium nitrate co-ingestion with protein does not augment postprandial muscle protein synthesis rates in older, type 2 diabetes patients

Kouw

Cermak

Burd

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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13 C]leucine-labeled protein with (PRONO3) or without (PRO) sodium nitrate (0.15 mmol/kg). Blood and muscle samples were collected to assess protein digestion and absorption kinetics and postprandial muscle protein synthesis rates. Upon protein ingestion, exogenous phenylalanine appearance rates increased in both groups (P Ͻ 0.001), resulting in 55 Ϯ 2% and 53 Ϯ 2% of dietary protein-derived amino acids becoming available in the circulation over the 5h postprandial period in the PRO and PRONO3 groups, respectively. Postprandial myofibrillar protein synthesis rates based on L-[ring-2 H5]phenylalanine did not differ between groups (0.025 Ϯ 0.004 and 0.021 Ϯ 0.007%/h over 0 -2 h and 0.032 Ϯ 0.004 and 0.030 Ϯ 0.003%/h over 2-5 h in PRO and PRONO3, respectively, P ϭ 0.7). No differences in incorporation of dietary protein-derived L-[1-13 C]phenylalanine into de novo myofibrillar protein were observed at 5 h (0.016 Ϯ 0.002 and 0.014 Ϯ 0.002 mole percent excess in PRO and PRONO3, respectively, P ϭ 0.8). Dietary nitrate co-ingestion with protein does not modulate protein digestion and absorption kinetics, nor does it further increase postprandial muscle protein synthesis rates or the incorporation of dietary protein-derived amino acids into de novo myofibrillar protein in older, type 2 diabetes patients. dietary nitrate; protein ingestion; aging; type 2 diabetes; anabolic resistance AGING IS ASSOCIATED with loss of skeletal muscle mass and strength, termed sarcopenia, and results in loss of functional capacity, a higher risk for hospitalization, and development of chronic metabolic diseases (33). Recently, we (20, 31), as well as others (25,35), showed that sarcopenia is more pronounced in older individuals with type 2 diabetes than in age-matched, normoglycemic controls. Since skeletal muscle tissue is a large site of postprandial glucose disposal, it is evident that the age-related loss of skeletal muscle mass is often accompanied by an insulin-resistant state (20,31,35).Maintenance of skeletal muscle mass is regulated by muscle protein synthesis and muscle protein breakdown rates. A chronic imbalance between muscle protein synthesis and muscle protein breakdown rates contributes to the accelerated loss of skeletal muscle mass with aging. It has been well established that protein ingestion and the associated increase in postprandial plasma amino acids in the circulation directly increase muscle protein synthesis rates (15,26,34,50). However, the postprandial stimulation of muscle protein synthesis following protein intake is impaired with aging, a phenomenon commonly referred to as anabolic resistance (15). This anabolic resistance to protein intake is considered to be a key factor in the progressive loss of skeletal muscle mass with aging. Although the factor(s) underpinning anabolic resistance remains unclear, age-related impairments in endothelium-dependent vasodilation and blood flow in response to nutrient (32) and exercise (19) stimuli are suggested to play a key role.The postprandial muscle protein synthetic re...

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Section: E330 Dietary Nitrate Co-ingestion and Muscle Protein Synthesiscontrasting

confidence: 82%

Sodium nitrate co-ingestion with protein does not augment postprandial muscle protein synthesis rates in older, type 2 diabetes patients

Kouw

Cermak

Burd

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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“…; Wijnands et al. ). This intervention resulted in a small but significant rise of MAP to 108% of control values (9 ± 2.5 mmHg increase, P = 0.007; Fig.…”

Section: Resultsmentioning

confidence: 98%

“…When plasma arginine was depleted acutely by ARG1 bolus injection, the arginine‐availability index dropped to ~25% of the original (Wijnands et al. ). In the present study, a similar intervention caused blood pressure to increase (Fig.…”

Section: Discussionmentioning

confidence: 99%

Deletion of endothelial arginase 1 does not improve vasomotor function in diabetic mice

et al. 2018

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Endothelial arginase 1 was ablated to assess whether this prevents hyperglycemia‐induced endothelial dysfunction by improving arginine availability for nitric oxide production. Endothelial Arg1‐deficient mice (Arg1‐KOT ie2) were generated by crossing Arg1 fl/fl (controls) with Tie2Cre tg/− mice and analyzed by immunohistochemistry, measurements of hemodynamics, and wire myography. Ablation was confirmed by immunohistochemistry. Mean arterial blood pressure was similar in conscious male control and Arg1‐KOT ie2 mice. Depletion of circulating arginine by intravenous infusion of arginase 1 or inhibition of nitric oxide synthase activity with L‐NG‐nitro‐arginine methyl ester increased mean arterial pressure similarly in control (9 ± 2 and 34 ± 2 mmHg, respectively) and Arg1‐KOT ie2 mice (11 ± 3 and 38 ± 4 mmHg, respectively). Vasomotor responses were studied in isolated saphenous arteries of 12‐ and 34‐week‐old Arg1‐KOT ie2 and control animals by wire myography. Diabetes was induced in 10‐week‐old control and Arg1‐KOT ie2 mice with streptozotocin, and vasomotor responses were studied 10 weeks later. Optimal arterial diameter, contractile responses to phenylephrine, and relaxing responses to acetylcholine and sodium nitroprusside were similar in normoglycemic control and Arg1‐KOT ie2 mice. The relaxing response to acetylcholine was dependent on the availability of extracellular l‐arginine. In the diabetic mice, arterial relaxation responses to endothelium‐dependent hyperpolarization and to exogenous nitric oxide were impaired. The data show that endothelial ablation of arginase 1 in mice does not markedly modify smooth muscle and endothelial functions of a resistance artery under normo‐ and hyperglycemic conditions.

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“…In fact, data suggest that oral supplementation of citrulline may be more efficient than oral arginine supplementation during inflammatory conditions 153 . Citrulline also increases plasma arginine levels in SCD 154 , 155 . Interestingly, in a pharmacokinetics study, we found that 10 g of oral glutamine significantly increased both glutamine and arginine bioavailability in patients with SCD at risk for pulmonary hypertension within 4 hours, 150 while glutamine‐enriched enteral nutrition (EN) improved arginine bioavailability in patients with multiple trauma 156 .…”

Section: Methods Of Providing Conditionally Essential Amino Acidsmentioning

confidence: 99%

Acquired Amino Acid Deficiencies: A Focus on Arginine and Glutamine

et al. 2017

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Nonessential amino acids are synthesized de novo and therefore not diet dependent. In contrast, essential amino acids must be obtained through nutrition since they cannot be synthesized internally. Several nonessential amino acids may become essential under conditions of stress and catabolic states when the capacity of endogenous amino acid synthesis is exceeded. Arginine and glutamine are 2 such conditionally essential amino acids and are the focus of this review. Low arginine bioavailability plays a pivotal role in the pathogenesis of a growing number of varied diseases, including sickle cell disease, thalassemia, malaria, acute asthma, cystic fibrosis, pulmonary hypertension, cardiovascular disease, certain cancers, and trauma, among others. Catabolism of arginine by arginase enzymes is the most common cause of an acquired arginine deficiency syndrome, frequently contributing to endothelial dysfunction and/or T-cell dysfunction, depending on the clinical scenario and disease state. Glutamine, an arginine precursor, is one of the most abundant amino acids in the body and, like arginine, becomes deficient in several conditions of stress, including critical illness, trauma, infection, cancer, and gastrointestinal disorders. At-risk populations are discussed together with therapeutic options that target these specific acquired amino acid deficiencies.

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Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity

Cited by 42 publications

References 60 publications

Sodium nitrate co-ingestion with protein does not augment postprandial muscle protein synthesis rates in older, type 2 diabetes patients

Sodium nitrate co-ingestion with protein does not augment postprandial muscle protein synthesis rates in older, type 2 diabetes patients

Deletion of endothelial arginase 1 does not improve vasomotor function in diabetic mice

Acquired Amino Acid Deficiencies: A Focus on Arginine and Glutamine

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