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.

The environmental footprint of animal food production is considered several-fold greater than that of crops cultivation. Therefore, the choice between animal and vegetarian diets may have a relevant environmental impact. In such comparisons however, an often neglected issue is the nutritional value of foods. Previous estimates of nutrients’ environmental footprint had predominantly been based on either food raw weight or caloric content, not in respect to human requirements. Essential amino acids (EAAs) are key parameters in food quality assessment. We re-evaluated here the environmental footprint (expressed both as land use for production and as Green House Gas Emission (GHGE), of some animal and vegetal foods, titrated to provide EAAs amounts in respect to human requirements. Production of high-quality animal proteins, in amounts sufficient to match the Recommended Daily Allowances of all the EAAs, would require a land use and a GHGE approximately equal, greater o smaller (by only ±1-fold), than that necessary to produce vegetal proteins, except for soybeans, that exhibited the smallest footprint. This new analysis downsizes the common concept of a large advantage, in respect to environmental footprint, of crops vs. animal foods production, when human requirements of EAAs are used for reference.

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.

Euglycemic insulin glucose-clamp and insulin-binding studies on erythrocytes and monocytes were performed in seven type II (non-insulin-dependent) diabetic subjects before and after 4 wk of metformin treatment (850 mg 3 times/day) and in five obese subjects with normal glucose tolerance. Glucose turnover was also measured at basal insulin concentrations and during hyperinsulinemic euglycemic clamps. During euglycemic insulin-glucose clamps, diabetic subjects showed glucose disposal rates of 3.44 +/- 0.42 and 7.34 +/- 0.34 mg X kg-1 X min-1 (means +/- SD) before metformin at insulin infusion rates of 0.80 and 15.37 mU X kg-1 X min-1, respectively. With the same insulin infusion rates, glucose disposal was 4.94 +/- 0.55 (P less than .01) and 8.99 +/- 0.66 (P less than .01), respectively, after metformin treatment. Glucose disposal rates in normal obese subjects were 5.76 +/- 0.63 (P less than .01) and 10.92 +/- 1.11 (P less than .01) at 0.80 and 15.37 mU X kg-1 X min-1, respectively. Insulin maximum binding to erythrocytes in diabetics was 9.6 +/- 4.2 and 5.8 +/- 2.6 X 10(9) cells (means +/- SD) before and after metformin treatment, respectively (NS). Insulin maximum binding to monocytes in diabetics was 6.2 +/- 2.3 X 10(7) cells before and 5.0 +/- 1.6% after metformin. Hepatic glucose production was higher in the diabetic patients at basal insulin levels, but not at higher insulin concentrations, and was not significantly changed by drug treatment. Basal glucose and insulin concentrations decreased with metformin. Thus, metformin treatment improved glucose disposal rate without significant effect on insulin-binding capacity on circulating cells.(ABSTRACT TRUNCATED AT 250 WORDS)

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.