PubMed Health⌕ Search

Biomedical subjects

R Barazzoni

Publications and source records attributed to R Barazzoni.

26 records · Page 2Linked to original sources
PubMed1996

Mechanisms of postprandial protein accretion in human skeletal muscle. Insight from leucine and phenylalanine forearm kinetics.

The relative role of protein synthesis and degradation in determining postprandial net protein deposition in human muscle is not known. To this aim, we studied forearm leucine and phenylalanine turnover by combining the arteriovenous catheterization with tracer infusions, before and following a 4 h administration of a mixed meal in normal volunteers. Forearm amino acid kinetics were assessed in both whole blood and plasma. Fasting forearm protein degradation exceeded synthesis (P < 0.01) using either tracer, indicating net muscle protein loss. The net negative forearm protein balance was quantitatively similar in whole blood and in plasma. After the meal, forearm proteolysis was suppressed (P < 0.05- < 0.03), while forearm protein synthesis was stimulated (P < 0.05- < 0.01). However, stimulation of protein synthesis was greater (P < 0.05- < 0.01) in whole blood (leucine data: +50.4 +/- 7.8 nmol/min x 100 ml of forearm; phenylalanine data: +30.4 +/- 11.6) than in plasma (leucine data: +17.8 +/- 5.6 nmol/min x 100 ml of forearm; phenylalanine data: +5.7 +/- 2.1). Consequently, the increment of net amino acid balance was approximately two to fourfold greater (P < 0.04- < 0.03) in whole blood than in plasma. In conclusion, meal ingestion stimulates forearm protein deposition through both enhanced protein synthesis and inhibited proteolysis. Plasma data underestimate net postprandial forearm protein synthesis, suggesting a key role of red blood cells and/or of blood mass in mediating mealenhanced protein accretion.

Adult↗
PubMed1996

The role of substrates in the regulation of protein metabolism.

Substrates are powerful modulators of amino acid and protein turnover in vivo (Table 4). Intravenous infusions of amino acids exert a protein-anabolic effect, because they directly inhibit endogenous protein degradation and stimulate protein synthesis at the whole-body level. A stimulation of protein synthesis has been observed also at the forearm level. These changes resulted in an improvement of body and tissue protein balance, which is the ultimate goal of any nutritional intervention aimed at preserving body protein stores. In humans acute intravenous infusions of carbohydrates do not appear to affect either protein degradation or leucine oxidation. However, animal studies support the view that glucose availability spares essential amino acids at least in the fetus. The effects of hypercaloric refeeding with high-carbohydrate diets may, however, result in increased protein turnover. Lipids, in the form of long-chain fatty acids, inhibit endogenous protein breakdown and may suppress leucine oxidation in the whole body. They do not affect protein synthesis. In contrast, medium-chain fatty acids apparently increased leucine oxidation, and therefore increased net protein catabolism. Ketone bodies may be anabolic provided that fatty acid concentrations are not concurrently decreased.

Amino Acids↗
PubMed1996

Response of phenylalanine and leucine kinetics to branched chain-enriched amino acids and insulin in patients with cirrhosis.

BACKGROUND & AIMS: We tested the effects of branched chain-enriched, aromatic-deficient amino acids with insulin to correct the altered protein turnover as well as phenylalanine (Phe) and leucine (Leu) rate of appearance in compensated cirrhotics and controls. METHODS: Phe and Leu tracers were infused both before and following intravenous amino acid administration with insulin and euglycemic clamp. RESULTS: In cirrhosis, fasting whole-body protein synthesis and protein degradation were normal; Phe rate of appearance was greater (P<0.05), whereas Leu rate of appearance/Phe rate of appearance ratio was approximately 35% less than in controls (P<0.001). Following the infusion, protein synthesis did not increase (+1% +/ 5% [NS] vs. +21% +/- 5% [P<0.05] in controls); protein degradation was more suppressed, whereas protein balance increased normally. Total Phe rate of appearance (0.91 +/- 0.13 micromol x kg-1 x min-1) and Leu/Phe disposal ratio (3.53 +/- 0.36) were nearly normalized (fasting controls, 0.68 +/- 0.07 micromol x kg-1 x min-1 and 2.87 +/- 0.14 micromol x kg-1 x min-1, respectively; P>0.05). However, Leu/Phe endogenous rate of appearance ration remained approximately 50% less (1.56 +/- 0.31 vs. 2.87 +/- 0.14; P<0.004) than in controls. CONCLUSIONS: Following this combined infusion in cirrhosis, net protein deposition increased normally despite a blunted response of protein synthesis. Phe and Leu to Phe peripheral disposal were near normalized; however, the exaggerated endogenous Phe production was not corrected entirely.

Amino Acids, Branched-Chain↗
PubMed1996

Protein degradation and synthesis measured with multiple amino acid tracers in vivo.

Whether tracers of different essential amino acids yield the same estimates of body protein turnover is still uncertain. Therefore, we have simultaneously determined leucine (Leu; using [14C]Leu), phenylalanine (Phe; using [13C]Phe), and tyrosine (Tyr; using [2H2]Tyr) rates of appearance (Ra) from proteolysis (PD), as well as Leu and Phe disposal, into protein synthesis (PS) both before and after an anabolic stimulus in healthy volunteers. Protein anabolism was stimulated by insulin plus a branched-chain amino acid-enriched aromatic amino acid-deficient amino acid solution, which increased Leu (from 145 +/- 9 to 266 +/- 10 mumol/l) but decreased Phe (from 57 +/- 2 to 46 +/- 3) and Tyr (from 58.7 +/- 5.5 to 21.0 +/- 2.2) concentrations. Postabsorptive endogenous Leu Ra (2.04 +/- 0.12 mumol.kg-1.min-1), Phe Ra (0.66 +/- 0.03), and Tyr Ra (0.45 +/- 0.06), as well as rates of PS determined with the leucine (1.65 +/- 0.10 mumol.kg-1.min-1) and the phenylalanine tracer (0.57 +/- 0.03), agreed well with the known abundance of these amino acids in body protein(s). After insulin and amino acids, PD was suppressed (P < 0.001) using all tracers. However, although percent suppression of endogenous Leu Ra (-->1.49 +/- 0.10 mumol.kg-1.min-1, 26 +/- 5%) and Phe Ra (-->0.53 +/- 0.02 mumol.kg-1.min-1, -20 +/- 2%) were comparable, endogenous Tyr Ra was suppressed to a larger extent (-->0.23 +/- 0.02 mumol.kg-1.min-1, -46 +/- 3% P = 0.038). PS was stimulated using the Leu (+24 +/- 7%, P < 0.02) but not the Phe (+6 +/- 4%, not significant) data. We conclude that isotopes of different essential amino acid: provide comparable estimates of PD and PS in the postabsorptive state. However, their responses to an anabolic stimulus may differ, possibly depending on exogenous amino acid availability and/or the resulting plasma levels.

Adult↗
PubMed1996

Hyperglucagonemia stimulates phenylalanine oxidation in humans.

Glucagon stimulates in vitro liver phenylalanine (Phe) degradation, thus inducing net protein catabolism. Whether these effects occur also in vivo in humans is not known. Therefore, we studied the effects of physiological hyperglucagonemia on Phe rate of appearance (Ra), hydroxylation, and oxidation in seven normal volunteers during infusions of somatostatin with replacement doses of insulin and growth hormone. Steady-state Phe kinetics were evaluated using the L-[1-14C]Phe tracer both at the end of a 3-h basal glucagon replacement period (glucagon concentration: 212 +/- 115 ng/l) and after a 3-h hormone infusion at the rate of approximately 3 ng x kg-1 x min-1 (--> 654 +/- 280 ng/l). Hyperglucagonemia did not change plasma Phe concentration and Ra but increased Phe oxidation by approximately 30% (P < 0.01). Oxidation was also increased by approximately 24% (P < 0.01) using plasma [14C]tyrosine (Tyr) specific activity as a precursor pool. Phe hydroxylation to Tyr estimated by assuming a fixed ratio of Tyr to Phe Ra (0.73) did not change. Nonhydroxylated Phe disposal decreased by approximately 6% (P = 0.08). These data show that in humans in the postabsorptive state, hyperglucagonemia, with near maintenance of basal insulin and growth hormone concentrations, stimulates Phe oxidation but not Phe hydroxylation, suggesting a different regulation of these two Phe catabolic steps. Glucagon may also reduce Phe availability for protein synthesis.

Adult↗
PubMed1995

A model of skeletal muscle leucine kinetics measured across the human forearm.

We propose a new six-compartment model of intracellular muscle kinetics of leucine and of its transamination product alpha-ketoisocaproic acid (KIC) by combining systemic tracer infusions of [14C]- and [15N]leucine with the arterial-deep venous catheterization of the human forearm. Venous [14C]KIC specific activity (SA) is taken as representative of intracellular [14C]leucine SA, whereas net [15N]leucine disposal is used to calculate leucine inflow and outflow across forearm cell membrane(s). In post-absorptive normal subjects, model-derived rates of intracellular leucine release from and incorporation into protein were approximately 32% (P = 0.03) and approximately 37% greater (P = 0.025), respectively, than those calculated using a conventional arteriovenous approach. Forearm fasting proteolysis exceeded protein synthesis (P < 0.025), whereas leucine oxidation was greater than zero (P < 0.01), suggesting a net negative leucine (i.e., protein) balance. Leucine inflow from blood to cell represented approximately 30% of arterial leucine delivery; therefore approximately 70% of arterial leucine bypassed intracellular metabolism. This model provides a comprehensive description of regional leucine and KIC kinetics and new estimates of protein degradation and synthesis across the human forearm.

Adult↗
PubMed1994

Fasting and postprandial phenylalanine and leucine kinetics in liver cirrhosis.

To investigate body protein turnover and the pathogenesis of increased concentration of plasma phenylalanine in liver cirrhosis, we have studied phenylalanine and leucine kinetics in cirrhotic (diabetic and nondiabetic) patients, and in normal subjects, both in the postabsorptive state and during a mixed meal, using combined intravenous and oral isotope infusions. Postabsorptive phenylalanine concentration and whole body rate of appearance (Ra) were approximately 40% greater (P < 0.05) in patients than in controls. Leucine concentrations were comparable, but intracellular leucine Ra was also increased (P < 0.05), suggesting increased whole body protein breakdown. Postprandial phenylalanine Ra was also greater (P < 0.05) in the patients. This difference was due to a diminished fractional splanchnic uptake of the dietary phenylalanine (approximately 40% lower in the cirrhotics vs. controls, P < or = 0.05). Postprandial leucine Ra was also increased in the patients, but splanchnic uptake of dietary leucine was normal. Thus both increased body protein breakdown and decreased splanchnic extraction of dietary phenylalanine can account for the increased phenylalanine concentrations in liver cirrhosis.

Adult↗