scholarly journals Plasma amino acid and metabolite signatures tracking diabetes progression in the UCD-T2DM rat model

2016 ◽  
Vol 310 (11) ◽  
pp. E958-E969 ◽  
Author(s):  
Brian D. Piccolo ◽  
James L. Graham ◽  
Kimber L. Stanhope ◽  
Oliver Fiehn ◽  
Peter J. Havel ◽  
...  

Elevations of plasma concentrations of branched-chain amino acids (BCAAs) are observed in human insulin resistance and type 2 diabetes mellitus (T2DM); however, there has been some controversy with respect to the passive or causative nature of the BCAA phenotype. Using untargeted metabolomics, plasma BCAA and other metabolites were assessed in lean control Sprague-Dawley rats (LC) and temporally during diabetes development in the UCD-T2DM rat model, i.e., prediabetic (PD) and 2 wk (D2W), 3 mo (D3M), and 6 mo (D6M) post-onset of diabetes. Plasma leucine, isoleucine, and valine concentrations were elevated only in D6M rats compared with D2W rats (by 28, 29, and 30%, respectively). This was in contrast to decreased plasma concentrations of several other amino acids in D3M and/or D6M relative to LC rats (Ala, Arg, Glu, Gln, Met, Ser, Thr, and Trp). BCAAs were positively correlated with fasting glucose and negatively correlated with plasma insulin, total body weight, total adipose tissue weight, and gastrocnemius muscle weight in the D3M and D6M groups. Multivariate analysis revealed that D3M and D6M UCD-T2DM rats had lower concentrations of amino acids, amino acid derivatives, 1,5-anhydroglucitol, and conduritol-β-opoxide and higher concentrations of uronic acids, pantothenic acids, aconitate, benzoic acid, lactate, and monopalmitin-2-glyceride relative to PD and D2W UCD-T2DM rats. The UCD-T2DM rat does not display elevated plasma BCAA concentrations until 6 mo post-onset of diabetes. With the acknowledgement that this is a rodent model of T2DM, the results indicate that elevated plasma BCAA concentrations are not necessary or sufficient to elicit an insulin resistance or T2DM onset.

2004 ◽  
Vol 82 (7) ◽  
pp. 506-514 ◽  
Author(s):  
Enoka P Wijekoon ◽  
Craig Skinner ◽  
Margaret E Brosnan ◽  
John T Brosnan

We investigated amino acid metabolism in the Zucker diabetic fatty (ZDF Gmi fa/fa) rat during the prediabetic insulin-resistant stage and the frank type 2 diabetic stage. Amino acids were measured in plasma, liver, and skeletal muscle, and the ratios of plasma/liver and plasma/skeletal muscle were calculated. At the insulin-resistant stage, the plasma concentrations of the gluconeogenic amino acids aspartate, serine, glutamine, glycine, and histidine were decreased in the ZDF Gmi fa/fa rats, whereas taurine, α-aminoadipic acid, methionine, phenylalanine, tryptophan, and the 3 branched-chain amino acids were significantly increased. At the diabetic stage, a larger number of gluconeogenic amino acids had decreased plasma concentrations. The 3 branched-chain amino acids had elevated plasma concentrations. In the liver and the skeletal muscles, concentrations of many of the gluconeogenic amino acids were lower at both stages, whereas the levels of 1 or all of the branched-chain amino acids were elevated. These changes in amino acid concentrations are similar to changes seen in type 1 diabetes. It is evident that insulin resistance alone is capable of bringing about many of the changes in amino acid metabolism observed in type 2 diabetes.Key words: plasma amino acids, liver amino acids, muscle amino acids, gluconeogenesis.


1979 ◽  
Vol 46 (1) ◽  
pp. 141-145 ◽  
Author(s):  
H. Freund ◽  
N. Yoshimura ◽  
J. E. Fischer

This study was designed to investigate whether exercise, when used as an adjunct to parenteral nutrition, has any influence on postoperative muscle catabolism, amino acid metabolism, and nitrogen balance. Twenty male Sprague-Dawley rats were divided into two groups of exercised and nonexercised animals. All animals underwent laparotomy and jugular vein cannulation, were placed in metabolic cages, and were infused with a dextrose-protein solution at 15 kcal and 0.56 g amino acids/100 g body wt per 24 h for a total of 96 h. The exercised animals were run on a treadmill for 15 min/day for a total of 3 days. There was no difference in nitrogen balance and body weight change between exercised and nonexercised animals, as well as no difference between animals who experienced different degrees of exercise. Total and individual plasma amino acids in the exercised group were 15% lower than in the nonexercised group; the total and individual free amino acids in muscle of the exercised group were 66% higher than in the nonexercised group. This pattern of high levels of amino acids in the muscle, coupled with decreased plasma concentrations, is suggestive of increased amino acid turnover in the muscle of the exercised animals. We suggest that, in the postoperative or postinjury period, exercise has a stimulating effect on amino acid turnover in the skeletal muscle resulting from 1) amino acid (mainly the branched-chain amino acids) consumption for energg metabolism and gluconeogenesis, and 2) protein synthesis. The net balance of both results in nitrogen equilibrium similar to that of a nonexercised control group.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sonia Yun Liu ◽  
Shemil P. Macelline ◽  
Peter V. Chrystal ◽  
Peter H. Selle

AbstractThe prime purpose of this review is to explore the pathways whereby progress towards reduced-crude protein (CP) diets and sustainable chicken-meat production may be best achieved. Reduced-CP broiler diets have the potential to attenuate environmental pollution from nitrogen and ammonia emissions; moreover, they have the capacity to diminish the global chicken-meat industry’s dependence on soybean meal to tangible extents. The variable impacts of reduced-CP broiler diets on apparent amino acid digestibility coefficients are addressed. The more accurate identification of amino acid requirements for broiler chickens offered reduced-CP diets is essential as this would diminish amino acid imbalances and the deamination of surplus amino acids. Deamination of amino acids increases the synthesis and excretion of uric acid for which there is a requirement for glycine, this emphasises the value of so-called “non-essential” amino acids. Starch digestive dynamics and their possible impact of glucose on pancreatic secretions of insulin are discussed, although the functions of insulin in avian species require clarification. Maize is probably a superior feed grain to wheat as the basis of reduced-CP diets; if so, the identification of the underlying reasons for this difference should be instructive. Moderating increases in starch concentrations and condensing dietary starch:protein ratios in reduced-CP diets may prove to be advantageous as expanding ratios appear to be aligned to inferior broiler performance. Threonine is specifically examined because elevated free threonine plasma concentrations in birds offered reduced-CP diets may be indicative of compromised performance. If progress in these directions can be realised, then the prospects of reduced-CP diets contributing to sustainable chicken-meat production are promising.


2002 ◽  
Vol 56 (10) ◽  
pp. 1259-1267 ◽  
Author(s):  
Cyril Petibois ◽  
Georges Cazorla ◽  
André Cassaigne ◽  
Gérard Déléris

Global metabolic adaptations to physical conditioning were described in 15 subjects by FT-IR spectrometry as the method allowed determination of glucose (Glc), lactate (La), glycerol, triglycerides (TG), fatty acyl moieties (FAM), and total amino acids plasma concentrations. Subtraction of plasma FT-IR spectra obtained at resting state from the exercise spectra also allowed determination of the biomolecular response to exercise. On week 1, exercise induced a transient hypoglycemia, a lactatemia increase of 153%, a FAM depletion of 27%, and a TG concentration decrease of 28%. Protein contents increased by 2%, but these were partly catabolized for amino acid supply (+27%), suggesting an important metabolic stress during exercise. On week 3, exercise hypoglycemia had disappeared, lactate increase was diminished by 91%, TG contents were decreased by 14%, and proteins and amino acids exhibited higher absorption increases. On week 5, TG and FAM concentrations were markedly increased during exercise, protein absorption was still increased (+9%), but amino acid blood release was diminished by 81%. These results described positive adaptations to training. Furthermore, FAM concentration could be determined from plasma FT-IR spectra by using the 2996–2819 cm−1 spectral area [ νas(CH3), νas(CH2), νs(CH3), and νs(CH2) absorbance; 0.82 mMol·L−1, a.u. cm−1], as well as for amino acid concentration by using the ν(COO−) spectral area (1430–1360 cm−1; 0.062 g·L−1, a.u. × cm−1). FT-IR spectrometry was useful to determine simultaneously various plasma concentrations and most of the biomolecular changes through successive samples.


1988 ◽  
Vol 254 (2) ◽  
pp. E187-E192
Author(s):  
T. A. Kotchen ◽  
G. P. Guthrie ◽  
L. D. Boucher ◽  
J. N. Lorenz ◽  
C. E. Ott

We evaluated the effects of selective dietary chloride loading (without sodium) on plasma renin activity (PRA) and plasma aldosterone in the sodium-deprived Sprague-Dawley rat. Three groups of animals were fed one of the following diets for 13 days: 1) low NaCl; 2) high NaCl; or 3) low sodium, high chloride, provided as glycine hydrochloride. Compared with NaCl-deprived animals, PRA and plasma aldosterone were lower (P less than 0.01) in animals fed low sodium high chloride, whereas aldosterone in animals fed glycine hydrochloride was higher (P less than 0.01) than that of NaCl-deprived animals. In contrast, plasma concentrations of corticosterone and 18-hydroxycorticosterone were not increased by selective chloride loading. Glycine chloride-fed animals were acidotic and had elevated plasma concentrations of potassium and ionized calcium. Thus stimulation of aldosterone by selective chloride loading is not related to PRA or ACTH but may be due to a direct effect of acidosis or an indirect effect of acidosis on potassium and/or calcium. Additionally, selective chloride loading appears to stimulate the conversion of 18-hydroxycorticosterone to aldosterone.


1990 ◽  
Vol 258 (5) ◽  
pp. F1288-F1294 ◽  
Author(s):  
M. B. Segal ◽  
J. E. Preston ◽  
C. S. Collis ◽  
B. V. Zlokovic

The kinetic constants and sodium independence of amino acid uptake by the basolateral face (blood side) of the isolated perfused choroid plexus of the sheep were investigated. Uptake of 3H-labeled L-alanine, glycine, L-glutamine, L-leucine, L-glutamate, and L-lysine was not significantly inhibited when the sodium level of the perfusate was lowered to less than 6 mM. The cerebrospinal fluid (CSF) secretion rate was, however, reduced by 65.6%. The Michaelis constants for L-serine, glycine, L-phenylalanine, L-glutamate, and L-arginine were measured and varied between 25.4 microM for L-arginine and 2.6 microM for L-glutamate. The Vmax for the amino acids varied by about the same range as Km, with L-serine having the highest Vmax of 28.8 nmol.min-1.g-1, and L-phenylalanine having the lowest at 4.6 nmol.min-1.g-1. At normal plasma concentrations of 30-155 microM for individual amino acids, the carriers for glycine, L-phenylalanine, and L-glutamate would be almost fully saturated (greater than 90%), while those for L-serine and L-arginine would be greater than 60% saturated. This restricted uptake of amino acids by the basolateral face of the choroid plexus, coupled to clearance of these substances out of the CSF (5), could account for the low levels in the CSF compared with that in the plasma.


1962 ◽  
Vol 202 (3) ◽  
pp. 577-583 ◽  
Author(s):  
William A. Webber

The effects of intravenous infusions of a variety of neutral and acidic amino acids on the plasma concentrations and excretions of naturally occurring amino acids were studied in dogs. Conventional clearance techniques were used, and the amino acid concentrations were determined by ion exchange column chromatography. Infusion of either l-glutamic acid or l-aspartic acid caused a gross increase in the plasma concentration and excretion of the other. Infusions of neutral amino acids including glycine, l-alanine, l-leucine, l-methionine, l-proline, and l-phenylalanine caused some minor changes in the endogenous plasma amino acid concentrations. They produced increases in the excretion of other neutral amino acids and, in some cases, of acidic and basic amino acids as well. In general, amino acids with long side chains were most effective in inhibiting reabsorption while cyclic side-chain compounds were less effective. There appear to be at least three somewhat separable mechanisms for renal tubular reabsorption of amino acids in dogs.


1982 ◽  
Vol 48 (3) ◽  
pp. 519-526 ◽  
Author(s):  
J. R. Mercer ◽  
E. L. Miller

1. The effect of supplementing barley diets with urea (U), extracted decorticated groundnut meal (GNM) or Peruvian fish meal (PFM) on plasma free amino acid concentrations in sheep have been examined and the first limiting amino acid has been indicated by measuring the changes in the concentration of the plasma essential amino acids (PEAA) during a rumen infusion of a volatile fatty acid (VFA) mixture.2. Three wethers fitted with rumen and re-entrant duodenal cannulas were given isonitrogenous, isoenergetic diets containing (g/kg dry matter (DM)) U 20, GNM 106 or PFM 78, the crude protein (nitrogen × 6.25) contents being 139, 145 and 148 respectively. The sheep were fed hourly, the mean daily dm intake being 0.634 kg.3. Plasma concentrations of valine, threonine, lysine, isoleucine and leucine were linearly related to their concentrations in duodenal digesta.4. A VFA mixture was infused into the rumen for 6 h to supply (mmol/min) acetate 1.47, propionate 0.22 and n-butyrate 0.27. Blood samples were taken 6 h before, during and 12 h after the end of the infusion.5. The concentration of all PEAA decreased relative to the pre-infusion and post-infusion controls but there were no significant differences between diets.6. The mean decreases in concentration averaged over all three diets showed that the decrease in concentration of methionine (41.5%) was far greater than for any other essential amino acid suggesting that under these conditions methionine was the first limiting amino acid.


1974 ◽  
Vol 31 (1) ◽  
pp. 47-57 ◽  
Author(s):  
A. K. Said ◽  
D. M. Hegsted ◽  
K. C. Hayes

1. Adult rats were fed on diets free of either lysine, methionine, threonine or protein. The threonine- and protein-deficient animals lost weight at approximately the same rate, about 100 g in 14 weeks, at which time several were moribund. In contrast, lysine-deficient animals lost only about 30 g in 14 weeks and had lost only 46 g after 22 weeks, when they were killed. Methionine-deficient animals showed an intermediate response. Losses in weight of several tissues – kidney, heart and two muscles – were related to, but not necessarily proportional to, the loss of body-weight. Liver weights relative to body-weights were large in lysine- and threonine-deficient animals and smallest in methionine-deficient animals.2. Adult rats were fed on diets containing zero, a moderate amount (about twice the estimated minimal requirement) or an excess (about four times the estimated requirement) of lysine or threonine in all combinations (3 × 3 design). Analysis of variance of the body-weights, tissue weights and tissue nitrogen contents indicated, in general, a significant effect of each amino acid, as expected, but also, in most instances, a significant interaction. Plasma concentrations of lysine and threonine were affected by the intakes of the respective amino acids, but plasma lysine concentrations were also affected by the threonine intake.3. Liver histology also suggested significant interactions between the two amino acids. Animals given no lysine but moderate amounts of threonine developed severely fatty livers; next most severely affected were animals receiving excess of both amino acids. Threonine deficiency, in the presence or absence of lysine, produced moderately fatty livers similar to those seen in protein-deficient animals.4. Since animals have varying ability to conserve body nitrogen when they are fed on diets limiting in different essential amino acids, measurements of biological value (BV) and net protein utilization by conventional methods, over a short period of time, over-estimate nutritive value relative to amino acid score and probably over-estimate the true nutritive value of poor-quality proteins, particularly those limiting in lysine. If so, this is a serious error, since it leads to underestimates of the protein requirements if BV is used. The fact that certain tissues, particularly the liver, do not necessarily lose nitrogen in proportion to total body nitrogen and may show specific pathological effects depending on the limiting amino acid or the proportions of amino acids in the diet also indicates that general measures of nitrogen economy may not be sufficiently discriminating tests of the nutritive value of proteins.


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