Effect of insulin-induced hypoglycemia on protein metabolism in vivo.

1990 ◽  
Vol 259 (3) ◽  
pp. E342 ◽  
Author(s):  
H Hourani ◽  
P Williams ◽  
J A Morris ◽  
M E May ◽  
N N Abumrad
Keyword(s):  
Amino Acids ◽  
Protein Metabolism ◽  
Conscious Dogs ◽  
Major Contributor ◽  
Leucine Kinetics ◽  
Significant Change ◽  
Plasma Leucine ◽  
Net Release ◽  
Oxidative Rate

The effects of insulin-induced hypoglycemia (IIH) on leucine kinetics (mumol.kg-1.min-1) and interorgan flow of amino acids (AA) were examined in 2 groups of 18-h fasted conscious dogs. Insulin was infused at 5 mU.kg-1.min-1 for 3 h. IIH (40 +/- 5 mg/dl) resulted in a drop in plasma leucine (114 +/- 10 to 64 +/- 9 microM) and leucine rate of appearance (Ra) (3.1 +/- 0.1 to 2.4 +/- 0.2) within 1 h but gradually increased (P less than 0.05) to 145 +/- 30 microM and 3.8 +/- 0.5 by 3 h. Leucine oxidative rate of disposal (Rd) increased from 0.44 +/- 0.08 to 1.02 +/- 0.35 (P less than 0.01), and nonoxidative Rd dropped initially but was near basal levels by 3 h. When euglycemia was maintained, there was sustained drop in plasma leucine from 122 +/- 12 to 42 +/- 6 mumol/l, leucine Ra from 3.1 +/- 0.4 to 1.8 +/- 0.2, oxidative Rd from 0.36 +/- 0.03 to 0.22 +/- 0.04, and nonoxidative Rd from 2.75 +/- 0.4 to 1.6 +/- 0.2 (all P less than 0.01). IIH was associated with a significant net release of leucine (and other AA) across the gut (0.04 +/- 0.05 to 1.86 +/- 0.30 mumol.kg-1.min-1; P less than 0.05). In the group with euglycemia there was no significant change in the gut balance of leucine. We conclude that IIH is associated with a proteolytic response and that the gut is the major contributor to this response.

Leucine as a regulator of whole body and skeletal muscle protein metabolism in humans

1992 ◽  
Vol 263 (5) ◽  
pp. E928-E934 ◽  
Author(s):  
K. S. Nair ◽  
R. G. Schwartz ◽  
S. Welle
Keyword(s):  
Amino Acids ◽  
Protein Degradation ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Plasma Concentrations ◽  
Essential Amino Acids ◽  
Whole Body ◽  
Skeletal Muscle Protein ◽  
Muscle Protein Metabolism

Leucine has been proposed as an in vivo regulator of protein metabolism, although the evidence for this in humans remains inconclusive. To test this hypothesis, we infused either L-leucine (154 +/- 1 mumol.kg-1 x h-1) or saline intravenously in six healthy men in two separate studies. L-Leucine infusion increased plasma concentrations of leucine and alpha-ketoisocaproate from 112 +/- 6 and 38 +/- 3 mumol/l to 480 +/- 27 (P < 0.001) and 94 +/- 13 mumol/l (P < 0.001), respectively, without any significant change in circulating insulin or C peptide levels. Leucine infusion decreased plasma concentrations of several amino acids and decreased whole body valine flux and valine oxidation (using L-[1-13C]valine as a tracer) and phenylalanine flux (using [2H5]-phenylalanine as a tracer). According to arteriovenous differences across the leg, the net balance of phenylalanine, valine, and lysine shifted toward greater retention during leucine infusion, whereas alanine balance did not change. Valine release and phenylalanine release from the leg (estimated from the dilution of respective tracers) decreased, indicating inhibition of protein degradation by leucine infusion. We conclude that leucine decreases protein degradation in humans and that this decreased protein degradation during leucine infusion contributes to the decrease in plasma essential amino acids. This study suggests a potential role for leucine as a regulator of protein metabolism in humans.

Effects of branched-chain-enriched amino acids and insulin on forearm leucine kinetics

1999 ◽  
Vol 97 (4) ◽  
pp. 437-448 ◽  
Author(s):  
Michela ZANETTI ◽  
Rocco BARAZZONI ◽  
Edward KIWANUKA ◽  
Paolo TESSARI
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Aromatic Amino Acids ◽  
Leucine Kinetics ◽  
Before And After ◽  
Amino Acid Mixtures ◽  
Leucine Transport ◽  
Branched Chain ◽  
Plasma Leucine

Although amino acid mixtures enriched in branched-chain amino acids (BCAA) and deficient in aromatic amino acids (AAA) are often used together with insulin and glucose in clinical nutrition, their physiological effects on muscle protein anabolism are not known. To this aim, we studied forearm leucine kinetics in post-absorptive volunteers, before and after the systemic infusion of BCAA-enriched, AAA-deficient amino acids along with insulin and the euglycaemic clamp. The results were compared with the effects of insulin infusion alone. A compartmental leucine forearm model was employed at steady state. Hyperaminoacidaemia with hyperinsulinaemia (to ≈ 80–100 μ-units/ml) increased the leucine plasma concentration (+70%; P< 0.001), inflow into the forearm cell (+150%; P< 0.01), disposal into protein synthesis (+100%; P< 0.01), net intracellular retention (P< 0.01), net forearm balance (by ≈ 6-fold; P< 0.01) and net deamination to α-ketoisocaproate (4-methyl-2-oxopentanoate) (+9%; P< 0.05). Leucine release from forearm proteolysis and outflow from the forearm cell were unchanged. In contrast, hyperinsulinaemia alone decreased plasma leucine concentrations (-35%; P< 0.001) and leucine inflow (-20%; P< 0.05) and outflow (-30%; P< 0.01) into and out of forearm cell(s), it increased net intracellular leucine retention (P< 0.03), and it did not change leucine release from forearm proteolysis (-20%; P = 0.138), net leucine deamination to α-ketoisocaproate, leucine disposal into protein synthesis or net forearm protein balance. By considering all data together, leucine disposal into protein synthesis was directly correlated with leucine inflow into the cell (r = 0.71; P< 0.0001). These data indicate that the infusion of BCAA-enriched, AAA-deficient amino acids along with insulin is capable of stimulating forearm (i.e. muscle) protein anabolism in normal volunteers by enhancing intracellular leucine transport and protein synthesis. These effects are probably due to hyperaminoacidaemia and/or its interaction with hyperinsulinaemia, since they were not observed under conditions of hyperinsulinaemia alone.

scholarly journals A double-isotope method for the measurement of ketone-body turnover in the rat. Effect of l-alanine

1984 ◽  
Vol 219 (1) ◽  
pp. 15-24 ◽  
Author(s):  
W D Reed ◽  
P J Baab ◽  
R L Hawkins ◽  
P T Ozand
Keyword(s):  
Amino Acids ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Isotope Method ◽  
Significant Change ◽  
Kinetics Of ◽  
Double Isotope

The synthesis of 4-3H-labelled ketone bodies, and their use along with 14C-labelled ketone-body precursors, is employed using an ‘in vivo’ rat infusion model to measure ketone-body turnover. The use of two isotopes is necessary to measure ketone-body turnover when ketogenesis may occur from more than one precursor such as glucose and fatty or amino acids. Requirements of isotopic equivalence in terms of metabolic similarity, valid stoichiometry and the lack of differences in the kinetics of relevant enzymes is demonstrated for the 4-3H- and 14C-labelled ketone bodies. The hypoketonaemic effect of L-alanine is shown by two distinct phases after the administration of L-alanine. During the first 12 min after alanine administration ther was a 50% decrease in acetoacetate and a 30% decrease in 3-hydroxybutyrate production, with no significant change in the utilization of either compound. The hypoketonaemic action of alanine during the following 16 min was primarily associated with an uptake of 3-hydroxybutyrate that was somewhat greater than the increase in its production. There were essentially equivalent decreases in production and utilization of acetoacetate, resulting in no significant net change in the level of this ketone body in the blood.

Leucine and phenylalanine kinetics during mixed meal ingestion: a multiple tracer approach

1992 ◽  
Vol 262 (4) ◽  
pp. E455-E463 ◽  
Author(s):  
G. Biolo ◽  
P. Tessari ◽  
S. Inchiostro ◽  
D. Bruttomesso ◽  
C. Fongher ◽  
...  
Keyword(s):  
Amino Acids ◽  
Steady State ◽  
Whole Body ◽  
Mixed Meal ◽  
Normal Volunteers ◽  
Dietary Amino Acids ◽  
Leucine Kinetics ◽  
Meal Ingestion

To estimate whole body and splanchnic metabolism of dietary amino acids, phenylalanine and leucine kinetics were determined simultaneously in six normal volunteers before and during the constant administration of a complete mixed meal, employing multiple tracers of these amino acids. L-[5,5,5-2H]leucine and L-[2,6-3H]-phenylalanine were infused intravenously; L-[1-13C]leucine and L-[1-14C]phenylalanine were administered orally with the meal. During the meal, steady-state leucine concentration rose from 136 +/- 6 to 190 +/- 14 mumol/l (P less than 0.01), phenylalanine from 44 +/- 4 to 61 +/- 6 mumol/l (P less than 0.01), total leucine rate of appearance (Ra) from 1.29 +/- 0.03 to 1.77 +/- 0.07 (P less than 0.01, +37 +/- 3%), and phenylalanine Ra from 0.73 +/- 0.05 to 0.80 +/- 0.07 mumol.kg-1.min-1 (P less than 0.05, +8 +/- 3%). Splanchnic uptake of dietary phenylalanine was greater (P less than 0.001) than that of leucine (58 +/- 4 vs. 25 +/- 4%, respectively), 44 +/- 3% of circulating leucine derived from the diet vs. 20 +/- 2% of circulating phenylalanine (P less than 0.01). Endogenous leucine and phenylalanine Ra were significantly suppressed (P less than 0.05). In summary: 1) splanchnic uptake of dietary phenylalanine is onefold greater than that of leucine; 2) dietary contribution to systemic phenylalanine Ra is about half of that to leucine Ra; and 3) endogenous appearance of both leucine and phenylalanine after the meal is suppressed. In conclusion, splanchnic metabolism of dietary leucine and phenylalanine differs markedly and can be quantitated in vivo without catheterization.

Role of leucine and other amino acids in regulating protein metabolism in vivo

1992 ◽  
Vol 262 (6) ◽  
pp. E925-E935 ◽  
Author(s):  
M. Frexes-Steed ◽  
D. B. Lacy ◽  
J. Collins ◽  
N. N. Abumrad
Keyword(s):  
Amino Acids ◽  
Experimental Period ◽  
Saline Group ◽  
Group Iii ◽  
Leucine Oxidation ◽  
Group I ◽  
Group Ii ◽  
Plasma Leucine ◽  
Independent Effects

The present study examines the independent effects of amino acids and leucine in modulating insulin's effect on leucine kinetics in 24-h fasted conscious dogs during an experimental period where insulin was infused at 600 mU.kg-1.h-1. Group I (n = 7) received saline, group II (n = 10) received sequential infusions of L-leucine at 0, 1, 3, and 1 mumol.kg-1.min-1 each lasting for 90 min, and group III (n = 6) received L-amino acids with doses of L-leucine matching those of group II. Plasma leucine (mumol/l) was 120 +/- 5 basally and 135 +/- 23 and 129 +/- 12 during the infusion of 3.0 mumol.kg-1.min-1 in groups II and III compared with 40 +/- 3 in group I. Leucine rate of appearance (mumol.kg-1.min-1) was 3.5 +/- 0.3 during the basal period and was suppressed 80% in both groups II and III as compared with 40% in group I (P less than 0.01). Leucine oxidation (basal = 0.7 +/- 0.15 mumol.kg-1.min-1) dropped 20% in group I but increased to threefold basal in group II and twofold in group III (P less than 0.05). Nonoxidative rate of disposal (basal = 2.6 +/- 0.2 mumol.kg-1.min-1) dropped 25% in group I and 55% in group II but did not change in group III. These data show that, in addition to insulin, amino acids and particularly leucine cause a marked suppression of proteolysis. Availability of all amino acids to prevent hypoaminoacidemia is necessary to sustain basal rates of protein synthesis. The infusion of leucine alone resulted in significant stimulation of leucine oxidation.

Ovine fetal leucine kinetics and protein metabolism during acute metabolic acidosis

1997 ◽  
Vol 272 (2) ◽  
pp. E275-E281
Author(s):  
J. R. Milley
Keyword(s):  
Amino Acids ◽  
Metabolic Acidosis ◽  
Fetal Growth ◽  
Protein Metabolism ◽  
Protein Breakdown ◽  
Leucine Uptake ◽  
Leucine Kinetics ◽  
Acute Metabolic Acidosis ◽  
Ovine Fetal ◽  
Fetal Acidosis

Fetal acidosis is associated with poor fetal growth. Because protein accretion is an important component of fetal growth, we used seven chronically prepared fetal lambs (10-16 days postoperation) to find whether fetal metabolic acidosis affected fetal protein accretion, and, if so, whether such effects were due to decreased synthesis or increased breakdown of proteins. Fetal leucine kinetics were measured during infusion of [1-(14)C]leucine by the reciprocal pool method. After control measurements, metabolic acidosis was induced by fetal infusion of 0.5 N HCl, and the measurements were repeated. Although fetal leucine concentration rose (164 +/- 11 vs. 216 +/- 15 microM; P < 0.001), fetal leucine uptake fell during acidosis (3.33 +/- 0.30 vs. 1.43 +/- 0.35 micromol x kg(-1) x min(-1); P < 0.05). However, the influx of leucine from protein breakdown increased (12.6 +/- 2.6 vs. 14.7 +/- 2.6 micromol x kg(-1) x min(-1); P < 0.02). The incorporation of leucine into fetal protein was unaffected by acidosis, so that fetal protein accretion fell (0.48 +/- 1.04 vs. -2.32 +/- 1.53 micromol x kg(-1) x min(-1); P < 0.001). Fetal leucine decarboxylation increased during acidosis (2.85 +/- 0.33 vs. 3.75 +/- 0.61 micromol x kg(-1) x min(-1); P < 0.05). We conclude that fetal metabolic acidosis stimulates pathways to degrade both protein and at least one of the subsequently derived amino acids, leucine. The consequence of such changes induced by acidosis is decreased protein accretion, a finding incompatible with normal fetal growth.

Effects of Androgenic Hormones on the Rate of Incorporation of Labeled Amino Acids in Male Adult Mice

1957 ◽  
Vol 191 (2) ◽  
pp. 306-312 ◽  
Author(s):  
Alfred Novak
Keyword(s):  
Amino Acids ◽  
Protein Metabolism ◽  
General Rule ◽  
Male Adult ◽  
Adult Mice ◽  
Muscle Tissues ◽  
Time Periods ◽  
Male Hormones ◽  
Male Hormone

Measurements of radioactivity were made on various tissues of the male mouse and the rates of in vivo incorporation of various radioactive amino acids into proteins were determined in intact, castrated, and male hormone-treated castrated mice. Using the rate of incorporation of radioactive amino acids into protein tissue as a criterion for protein metabolism, male hormones at physiological dosages produced no significant protein anabolic effect in visceral and muscle tissues of the mice studied. As a general rule, the castrated mice incorporated more radioactive amino acids than intact animals. Incorporation of radioactive histidine however in longer time periods appeared to follow a somewhat different pattern, i.e., the male hormone showed a stimulating action in both intact and hormone-treated castrates.

On the Role of Branched-Chain Amino Acids in Protein Turnover of Skeletal Muscle. Studies in vivo with L-Norleucine

1985 ◽  
Vol 40 (5-6) ◽  
pp. 427-437 ◽  
Author(s):  
Klaus-Joachim Schott ◽  
Jochen Gehrmann ◽  
Ulla Potter ◽  
Volker Neuhoff
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Small Intestine ◽  
Amino Acid ◽  
Protein Metabolism ◽  
Protein Turnover ◽  
Protein Concentration ◽  
Amino Acid Concentrations

Abstract 1. The effect of ʟ-norleucine, an isomer of leucine, on protein metabolism in vivo was studied in suckling rats. Rats were injected subcutaneously with various doses of ʟ-norleucine (0.5 and 5.0 μmol/g body wt.) every 12 h from 3 to 15 days post partum. Protein concentration, amino acid concentrations, and incorporation of [3H]tyrosine into protein were analyzed in liver, muscles of thigh and small intestine. Amino acid concentrations and insulin levels in serum were also measured. 2. At 5 days of age, norleucine induced an increase in protein concentration of skeletal muscle with an increased incorporation of [3H]tyrosine into protein indicating an accelerated protein synthesis. Changes in protein metabolism were paralleled by alterations in the amino acid pattern of this tissue. 3. When protein concentration and protein synthesis were increased in skeletal muscle, protein concentration of small intestine was decreased, accompanied by elevated levels of amino acids in tissue. Protein synthesis of small intestine was not altered by the norleucine treatment. The results suggest a close interrelationship between skeletal muscle and small intestine with respect to protein turnover. 4. The effects of norleucine were less pronounced at 10 and 15 days of age, which indicates a metabolic adaptation to the treatment. 5. Alterations in amino acid concentrations of tissue due to changes in protein metabolism were not uniform but tissue-specific. 6. Current concepts for explaining the effects of branched-chain amino acids (BCAA) on protein turnover in skeletal muscle are based on the assumption that the BCAA or leucine alone might become rate-limiting for protein synthesis in muscle under catabolic conditions. The amino acid analogue norleucine, however, cannot replace any of the BCAA in protein. Additionally, norleucine affected protein metabolism in highly anabolic organisms. Therefore, the present thoughts on this issue appear to be incomplete.

scholarly journals THE PLACENTA AND PROTEIN METABOLISM

1955 ◽  
Vol 101 (6) ◽  
pp. 617-626 ◽  
Author(s):  
G. H. Whipple ◽  
R. B. Hill ◽  
R. Terry ◽  
F. V. Lucas ◽  
C. L. Yuile
Keyword(s):  
Amino Acids ◽  
Oral Administration ◽  
Plasma Protein ◽  
Protein Metabolism ◽  
Plasma Proteins ◽  
Maternal Plasma ◽  
Blue Dye ◽  
Placental Function ◽  
Length Of Gestation

Plasma proteins tagged in vivo by feeding D-L-lysine-ϵ-C14 to donor dogs have been administered to pregnant dogs by both oral and intravenous routes. A relatively small percentage of the C14 activity originally incorporated in these proteins is found to pass from mother to fetus after intravenous injection. The amount transferred tends to increase with the length of gestation period and total number of fetuses. Plasma protein labeled with I131 does not cross the placenta in the dog, but does in the rabbit. Evans blue dye does not cross the placenta of the dog. After oral administration of labeled plasma protein or lysine, C14 is transferred promptly and in considerable quantity to the fetus. Labeled plasma proteins disappear more rapidly from the circulation of pregnant than of normal dogs. This increased metabolic turnover occurs without excretion of any excess waste metabolites. The chorionic epithelium, gram for gram, is probably 2 to 3 times as active as the hepatic epithelium in protein metabolism. These findings indicate an important placental function related to maternal and fetal protein metabolism. While the placenta utilizes maternal plasma proteins and amino acids, in a quantitative sense the latter appear to supply the major nitrogen needs of the growing fetus.

Sign in / Sign up

Export Citation Format

Share Document