The effect of insulin deficiency, dietary protein intake, and plasma amino acid concentrations on brain amino acid levels in rats

1985 ◽  
Vol 63 (5) ◽  
pp. 487-494 ◽  
Author(s):  
N. Theresa Glanville ◽  
G. Harvey Anderson

The effect of diabetes (streptozotocin, 65 mg/kg ip), dietary protein intake (15–60%), and plasma amino acid concentrations on brain large neutral amino acid levels in rats was examined. After 20 days, the plasma concentrations of methionine and the branched chain amino acids (BCAA), valine, isoleucine, and leucine were increased in diabetic rats. In brain tissue, methionine and valine levels were increased but threonine, tyrosine, and tryptophan concentrations were depressed. Increased protein consumption promoted a diabetic-like plasma amino acid pattern in normal rats while enhancing that of diabetic animals. However, with the exception of threonine, glycine, valine, and tyrosine, there was little effect on brain amino acid levels. A good association was found between the calculated brain influx rate and the actual brain concentration of threonine, methionine, tyrosine, and tryptophan in diabetic animals. There was no correlation, however, between brain influx rate and brain BCAA levels. Thus, the brain amino acid pattern in diabetes represents the combined effects of insulin insufficiency and composition of the diet ingested on plasma amino acid levels as well as metabolic adaptation within the brain itself.

1990 ◽  
Vol 258 (5) ◽  
pp. R1095-R1100 ◽  
Author(s):  
B. S. Daniels ◽  
T. H. Hostetter

Vasoactive hormonal response to two levels of dietary protein intake was studied in seven healthy adult volunteers. The subjects were randomly placed on a 2-g.kg-1.day-1 (high) or 0.55-g.kg-1.day-1 (low) diet using a crossover design and were studied on the morning of the 5th day and again after 24 h of indomethacin treatment. Plasma renin activity (PRA), aldosterone, vasopressin, and urinary excretion of 6-ketoprostaglandin F1 alpha (PGF1 alpha) were significantly higher on the high-protein diet despite constancy of body weight, blood pressure, pulse, urinary sodium and potassium excretion, and plasma amino acid levels. After treatment with cyclooxygenase inhibitor indomethacin, 6-keto-PGF1 alpha excretion was equalized, but the elevated PRA and aldosterone levels persisted on the high-protein diet, suggesting that PRA and aldosterone elevations do not depend entirely on prostanoid release. We conclude that chronic augmentation of dietary protein intake is accompanied by alterations of vasoactive hormones, which persist for up to 10 h postprandially and are independent of elevated plasma amino acid levels. Such hormonal alterations may mediate some of the dietary protein-mediated changes in renal hemodynamics.


Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1543 ◽  
Author(s):  
Naomi Yoshii ◽  
Koji Sato ◽  
Riki Ogasawara ◽  
Yusuke Nishimura ◽  
Yasushi Shinohara ◽  
...  

Dietary protein intake is critical for the maintenance of skeletal muscle mass. Plasma amino acid concentrations increase with protein intake and increases in muscle protein synthesis are dependent on leucine concentrations. We aimed to investigate the effect of a mixed meal and free amino acids intake on plasma leucine concentrations. In this randomized crossover study, 10 healthy young men (age 25 ± 1 years, height 1.73 ± 0.02 m, weight 65.8 ± 1.5 kg) underwent tests under different conditions—intake of 2 g of leucine (LEU), intake of a mixed meal (protein 27.5 g, including 2.15 g of leucine, protein: fat: carbohydrate ratio—22:25:53) only (MEAL), intake of 2 g of leucine immediately after a mixed meal (MEAL-LEU) and intake of 2 g of leucine 180 min after a mixed meal (MEAL-LEU180). Blood samples were collected within 420 min (240 min for LEU only) after intake and changes in amino acid concentrations were evaluated. Although the maximum plasma leucine concentration increased to 442 ± 24 µM for LEU, it was lower at 347 ± 16 µM (p < 0.05 vs. LEU) for MEAL-LEU, 205 ± 8 µM (p < 0.05 vs. LEU) for MEAL. The maximum plasma leucine concentration for MEAL-LEU180 increased to 481 ± 27 µM and compared to LEU there was no significant difference (p > 0.1). The observation that rapid elevations in plasma leucine concentrations are suppressed when leucine is ingested at the same time as a meal suggests that the timing of its intake must be considered to maximize the anabolic response.


1981 ◽  
Vol 240 (6) ◽  
pp. E712-E721 ◽  
Author(s):  
K. J. Motil ◽  
D. E. Matthews ◽  
D. M. Bier ◽  
J. F. Burke ◽  
H. N. Munro ◽  
...  

Whole-body leucine and lysine metabolism was explored in young adult men by a primed constant intravenous infusion of a mixture of L-[1–13C]leucine and L-[alpha-15N]lysine over a 4-h period. Subjects were studied after an overnight fast (postabsorptive state) or while consuming hourly meals (fed state) after adaptation to diets providing either a surfeit level of protein (1.5 g.kg body-1.day-1), a level approximating maintenance requirements (marginal intake) (0.6 g.kg body wt-1.day-1), or a grossly inadequate level (0.1 g.kg-1.day-1). The change in protein intake from a marginal to a surfeit level was associated with an increased leucine flux and incorporation of leucine into body protein. In the fed state, oxidation of leucine increased sharply and release of leucine from tissue protein diminished. When dietary protein intake was reduced from the requirement to inadequate level, leucine flux and body protein synthesis and protein breakdown were reduced, together with a smaller reduction in leucine oxidation. The response of the metabolism of [15N]lysine was responsible for maintenance of leucine and other essential amino acid economy, and they appear to be related to the nitrogen and amino acid requirements of the subject. These findings also demonstrate an effect of meals, modulated by their protein content, on the dynamics of whole-body amino acid metabolism.


2019 ◽  
Vol 109 (3) ◽  
pp. 517-525 ◽  
Author(s):  
Casey M Rebholz ◽  
Zihe Zheng ◽  
Morgan E Grams ◽  
Lawrence J Appel ◽  
Mark J Sarnak ◽  
...  

ABSTRACT Background Accurate assessment of dietary intake is essential, but self-report of dietary intake is prone to measurement error and bias. Discovering metabolic consequences of diets with lower compared with higher protein intake could elucidate new, objective biomarkers of protein intake. Objectives The goal of this study was to identify serum metabolites associated with dietary protein intake. Methods Metabolites were measured with the use of untargeted, reverse-phase ultra-performance liquid chromatography–tandem mass spectrometry quantification in serum specimens collected at the 12-mo follow-up visit in the Modification of Diet in Renal Disease (MDRD) Study from 482 participants in study A (glomerular filtration rate: 25–55 mL · min−1 · 1.73 m−2) and 192 participants in study B (glomerular filtration rate: 13–24 mL · min−1 · 1.73 m−2). We used multivariable linear regression to test for differences in log-transformed metabolites (outcome) according to randomly assigned dietary protein intervention groups (exposure). Statistical significance was assessed at the Bonferroni-corrected threshold: 0.05/1193 = 4.2 × 10−5. Results In study A, 130 metabolites (83 known from 28 distinct pathways, including 7 amino acid pathways; 47 unknown) were significantly different between participants randomly assigned to the low-protein diet compared with the moderate-protein diet. In study B, 32 metabolites (22 known from 8 distinct pathways, including 4 amino acid pathways; 10 unknown) were significantly different between participants randomly assigned to the very-low-protein diet compared with the low-protein diet. A total of 11 known metabolites were significantly associated with protein intake in the same direction in both studies A and B: 3-methylhistidine, N-acetyl-3-methylhistidine, xanthurenate, isovalerylcarnitine, creatine, kynurenate, 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE (P-16:0/20:4), 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (P-18:0/20:4), 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC (P-16:0/20:4), sulfate, and γ-glutamylalanine. Conclusions Among patients with chronic kidney disease, an untargeted serum metabolomics platform identified multiple pathways and metabolites associated with dietary protein intake. Further research is necessary to characterize unknown compounds and to examine these metabolites in association with dietary protein intake among individuals without kidney disease. This trial was registered at clinicaltrials.gov as NCT03202914.


1975 ◽  
Vol 34 (2) ◽  
pp. 259-265 ◽  
Author(s):  
T. C. Marrs ◽  
Jill M. Addison ◽  
D. Burston ◽  
D. M. Matthews

1. Plasma amino acid levels have been estimated at 0, 15, 30 and 45 min after ingestion of doses of (1) an amino acid mixture simulating casein and (2) a tryptic hydrolysate of casein consisting mainly of oligopeptides. Both doses contained the same amount of nitrogen.2. After ingestion of both preparations, there was a prompt increase in plasma amino acid levels, followed by a decrease. No such change occurred in fasting subjects. There were no significant differences between increments in plasma amino acid levels after ingestion of the amino acid mixture and the corresponding increments after ingestion of the tryptic hydrolysate.3. Correlations were found between the areas under the curves for individual amino acid concentrations, after ingestion of the two preparations, and the amino acid composition of casein. The results do not suggest that increases in plasma amino acid levels following small doses of protein digestion products are the result of circadian changes, or that such increases are ‘swamped’ by absorption of amino acids from endogenous protein in the lumen of the small intestine.


2016 ◽  
Vol 53 (4) ◽  
pp. 380
Author(s):  
Sarita Devi ◽  
Tinku Thomas ◽  
Pratibha Dwarkanath ◽  
Annamma Thomas ◽  
C. N. Sheela ◽  
...  

Low intakes of quality dietary protein could affect the methionine cycle during pregnancy, which is important for fetal growth and epigenetic regulations. Since low quality protein intake is prevalent in India, it is important to define biomarkers of the low protein intake, specifically of methyl cycle homeostasis. A secondary analysis of data was performed, from a randomized intervention trial with 500 ml milk/d on south Indian pregnant women, to examine the association of dietary protein intake with concentrations of specific amino acids (methionine, glycine and serine). The subjects also underwent isotopic infusions (n = 52) for the measurement of amino acid kinetics. Dietary intakes were measured each week by multiple 24 h recall until delivery. The plasma concentrations of amino acids (methionine, serine and glycine) were compared with kinetics of methionine i.e. transmethylation, remethylation and transulfuration (TM, RM, TS) and serine to glycine conversion rates, as measured by stable isotope labeled amino acid infusion. Dietary protein intake in the 3<sup>rd</sup> trimester correlated positively with intakes of milk and milk based food products (ρ=0.52, p&lt;0.001) and methionine (ρ=0.97, p&lt;0.001) and with gestational weight gain (GWG, ρ=0.32, p=0.044). While the methionine concentration did not correlate with methyl cycle flux parameters (TM, RM and TS), the plasma concentrations of conditionally essential serine and glycine were positively correlated with their respective flux rate and with RM, TM and TS rates. Further, glycine concentrations specifically correlated positively with serine to glycine conversion rates (ρ=0.32, p=0.027). Dietary protein and methionine supply are important for the conservation of methionine during pregnancy. This had an effect on GWG, but not on birth weight, though this may have been due to the relatively small sample size. The plasma concentration of glycine was correlated with the serine-glycine conversion, which affords methyl groups for the body and supplies these when dietary protein/methionine is in poor supply. This indicates that itcan act as a biomarker of the serine-glycine conversion flux rate, which increases in the presence of a poor protein supply. In general, the plasma concentrations of these conditionally essential amino acids may be biomarkers of the methyl cycle during pregnancy, but this needs to be tested in a larger sample.


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