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The effects of nonprotein energy source (ie, glucose only vs glucose and lipid) on nitrogen retention and total-body protein turnover were studied in 20 parenterally fed newborn infants. All infants received approximately 3 g amino acids and 80-90 kcal.kg body wt.d. Total-body protein synthesis was estimated by using three constant-infusion, end-product methods: enrichment of urinary urea and ammonia in response to a [15N]glycine label and exhaled carbon dioxide enrichment in response to a [1-13C]leucine label. No differences were seen in nitrogen retention between the two energy sources. The estimate of total-body protein turnover obtained from the 13C label was similar to that obtained with the [15N]urea label. No differences in turnover rates were observed between the two diet groups. Use of the glucose-plus-lipid fuel system enhanced energy storage and the reutilization of amino acid for protein synthesis.

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Increased dietary protein provided as purified casein augments renal endothelin production (JASN 2004;15:2266) by mechanisms that have not been fully elucidated. We tested the hypothesis that augmented renal endothelin production induced by dietary protein as casein is mediated by the acid challenge to systemic acid-base status induced by metabolism of this protein source. Munich-Wistar rats ate minimum electrolyte diets with protein provided as either casein (CAS) that yields net acid or soy that yields net base when metabolized. After 3 weeks of diet we measured blood and urine acid-base data, urine endothelin-1 (ET-1) excretion as a surrogate of renal ET-1 production, and renal cortical endothelin-1 mRNA with real-time PCR and light cycler technology. Within groups eating the two protein types, those eating diets with higher protein content (50%) were compared to those eating 20% protein, the latter % being comparable to standard rat chow. Animals eating 50% compared to 20% CAS had lower serum total CO2 (23.3 ± 0.5 vs. 25.2 ± 0.6 mM, p < .03), higher urine net acid excretion (NAE) (7067 ± 937 vs. 4460 ± 639 μM/d, p < .04), and higher urine ET-1 excretion (70 ± 14 vs. 22 ± 3 pg/day, p < .005). By contrast, total CO2 (27.3 ± 0.6 vs. 26.6 ± 0.7 mM, p = .78), urine NAE (1698 ± 247 vs. 1803 ± 332 μM/d, p = .80), and urine ET-1 excretion (42 ± 10 vs. 37 ± 3 pg/day, p = .64) were not higher in animals eating 50% compared to 20% soy. ET-1 mRNA was higher in 50% vs. 20% CAS but was similar in 50% vs. 20% soy. 50% CAS animals given oral bosentan, an endothelin A/B receptor antagonist, had higher serum total CO2 (24.8 ± 0.5 vs. 23.3 ± 0.4 mM, p < .04, paired t) and lower urine NAE (7067 ± 937 to 5704 ± 594 μM/d, p < .05, paired t) than 50% CAS animals not given bosentan. Serum total CO2 and urine NAE were not different in the bosentan-ingesting vs. non-ingesting 20% CAS or in either soy group. The data show that increasing dietary protein with the acid-producing casein diet but not with the base-producing soy diet increases renal endothelin production and induces endothelin-mediated augmentation of renal acidification. The data support the hypothesis that augmented renal endothelin production induced by increased dietary protein as casein is medicated through the acid challenge to systemic acid-base status provided by the casein diet.

To assess the effects of artificial beta-cell-directed insulin therapy on protein metabolism in patients with diabetes mellitus, nitrogen balance, urea production, and whole body protein turnover were determined in five type I insulin-dependent subjects and five age- and sex-matched controls. Each diabetic participant was studied over two 4-day periods while receiving conventional insulin therapy (one or two daily injections of short and intermediate acting insulin) or insulin delivered by the artificial beta-cell. While the diabetic participants received conventional insulin therapy, nitrogen balance, urea production, whole body protein turnover, and protein synthesis and breakdown rates did not differ significantly from the control group. However, when the same subjects were on artificial beta-cell-directed insulin therapy, they manifested a significant net positive nitrogen balance of over 2 g/day. This change in nitrogen balance was largely due to a fall in urea nitrogen production from 174 +/- 6 to 140 +/- 13 mg/kg body weight per day (p less than 0.05). In addition, while artificial beta-cell therapy did not affect whole body protein turnover or breakdown rates, a significant rise (2.1 +/- 0.2 to 2.4 +/- 0.1 g/kg per day) in whole body protein synthesis was observed (p less than 0.05). Thus when compared to conventional insulin treatment, artificial beta-cell-directed insulin therapy was associated with a 14% increase in the rate of protein synthesis and a decrease of 20% in urea nitrogen production, leading to a net positive nitrogen balance.