Chronic metabolic acidosis decreases albumin synthesis and induces negative nitrogen balance in humans.

Chronic metabolic acidosis has been previously shown to stimulate protein degradation. To evaluate the effects of chronic metabolic acidosis on nitrogen balance and protein synthesis we measured albumin synthesis rates and urinary nitrogen excretion in eight male subjects on a constant metabolic diet before and during two different degrees of chronic metabolic acidosis (NH4Cl 2.1 mmol/kg body weight, low dose group, and 4.2 mmol/kg body weight, high dose group, orally for 7 d). Albumin synthesis rates were measured by intravenous injection of [2H5ring]phenylalanine (43 mg/kg body weight, 7.5 atom percent and 15 atom percent, respectively) after an overnight fast. In the low dose group, fractional synthesis rates of albumin decreased from 9.9 +/- 1.0% per day in the control period to 8.4 +/- 0.7 (n.s.) in the acidosis period, and from 8.3 +/- 1.3% per day to 6.3 +/- 1.1 (P < 0.001) in the high dose group. Urinary nitrogen excretion increased significantly in the acidosis period (sigma delta 634 mmol in the low dose group, 2,554 mmol in the high dose group). Plasma concentrations of insulin-like growth factor-I, free thyroxine and tri-iodothyronine were significantly lower during acidosis. In conclusion, chronic metabolic acidosis causes negative nitrogen balance and decreases albumin synthesis in humans. The effect on albumin synthesis may be mediated, at least in part, by a suppression of insulin-like growth factor-I, free thyroxine and tri-iodothyronine.

Responsiveness of muscle protein synthesis to growth hormone administration in HIV-infected individuals declines with severity of disease.

This study was undertaken to determine if human recombinant growth hormone (hrGH, 6 mg/d for 2 wk) would stimulate muscle protein synthesis in AIDS wasting. Healthy controls were compared with patients who were HIV+, had AIDS without weight loss, and had AIDS with > 10% weight loss. Before hrGH, rates of skeletal muscle protein synthesis, measured with l-[2H5]phenylalanine, were the same in controls and in all stages of disease. Rates of myofibrillar protein degradation, however, assessed from urinary excretion of 3-methyl histidine, were higher in AIDS and AIDS wasting than in HIV+ or healthy individuals. The group with weight loss had significantly higher TNFalpha levels but not higher HIV viral loads. Muscle function, as determined by isokinetic knee extension and shoulder flexion, was significantly higher in controls than all infected individuals. After GH, rates of protein synthesis were stimulated 27% in controls, with a smaller increase (11%) in HIV+, and a significant depression (42%) in AIDS with weight loss, despite fourfold elevation in insulin-like growth factor-I in all groups. There was a significant correlation of hrGH-induced changes in muscle protein synthesis with severity of disease (P = 0.002). The results indicate increased basal muscle protein degradation and decreased responsiveness of muscle protein synthesis to GH in the later stages of disease.

Non-surgical alternatives to invasive procedures in mice.

We have developed and validated catheterization protocols in mice that allow for simultaneous infusion and sampling. A sampling catheter was inserted in the lateral vein of the tail, while the animals were infused either intravenously or intragastrically through a second catheter placed in the contralateral lateral vein or via an intragastric catheter, respectively. The applicability of these methods of infusion and blood sampling were validated by conducting urea kinetics utilizing stable isotopes. These non-surgical procedures are non-invasive, inexpensive, fast to perform and animals do not require a recovery period before their use.

Protein synthesis in liver and skeletal muscle of mice bearing an ascites tumor.

In mice bearing an ascites tumor at an advanced stage of growth, the weight of the gastrocnemius muscle fell, whereas that of the liver increased. Fractional rates of protein synthesis were measured in vivo under conditions designed to minimize uncertainties in the determination of the specific radioactivity of the precursor amino acid pool. Protein synthesis in liver increased in the tumor-bearing mice in comparison with controls either fed ad libitum or pair-fed to the reduced food intake of the tumor-bearing group. In muscle, the rate of protein synthesis fell substantially in comparison to ad libitum-fed controls but was not significantly different from that in a group for which food intake was restricted to that of the tumor-bearing animals.

Increased protein turnover despite normal energy metabolism and responses to feeding in patients with lung cancer.

We have examined the responses of energy and protein metabolism to nutrient intake in nine patients with lung carcinoma, of whom none were cachexic and only one had distant metastases, compared with nine control patients for elective aneurysm surgery, who were comparable in terms of age, body mass index, and smoking habits. Whole-body protein turnover and leucine oxidation were assessed by primed continuous infusion of L-[13C]leucine. Indirect calorimetry was used to determine energy expenditure and rates of carbohydrate and fat utilization. Lean body mass (LBM) was estimated from dilution of deuterium oxide. Measurements were made over an 8-h period, including 4 h postabsorptive followed by 4 h of feeding, during which small hourly meals were consumed. In the post-absorptive state, the rate of incorporation of leucine into protein was higher in the cancer group (mean +/- SD, cancer versus control: 102 +/- 21 versus 86 +/- 8 mumol/kg LBM/h, P less than 0.05), as was the release of leucine by protein degradation (126 +/- 19 versus 110 +/- 10 mumol/kg LBM/h, P less than 0.01), but there was no difference in rates of leucine oxidation (27 +/- 6 versus 27 +/- 5 mumol/kg LBM/h) or leucine balance (-25 +/- 7 versus -24 +/- 4 mumol/kg LBM/h). There were no differences between the cancer and control groups with respect to either resting energy expenditure (37.3 +/- 3.5 versus 35.2 +/- 3.8 kcal LBM/day) or the postabsorptive pattern of nutrient utilization (61 +/- 13% fat, 26 +/- 10% carbohydrate, and 13 +/- 2% protein versus 65 +/- 7%, 21 +/- 7%, and 14 +/- 2%, respectively). During feeding, leucine oxidation rose relative to the postabsorptive state, incorporation into protein remained the same, and release by protein degradation fell. Incorporation (106 +/- 20 versus 89 +/- 7 mumol/kg LBM/h, P less than 0.05) and release (59 +/- 12 versus 42 +/- 14 mumol/kg LBM/h, P less than 0.02) remained higher in the cancer group than in controls, but leucine oxidation (43 +/- 15 versus 43 +/- 12 mumol/kg LBM/h) and leucine balance (+48 +/- 10 versus +47 +/- 12 mumol/kg LBM/h) were the same. Energy expenditure during feeding increased to 43.8 +/- 5.1 versus 43.2 +/- 4.2 kcal/kg LBM/day, derived from 32 +/- 11% fat, 52 +/- 9% carbohydrate, and 16 +/- 5% protein in cancer patients and 36 +/- 7%, 48 +/- 8%, and 16 +/- 4%, respectively, in controls.(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of rejuvenation of aged erythrocytes on biochemical parameters in the perfused hind limb muscle preparation.

(1) A systematic investigation was carried out into the use of time-expired erythrocytes in an isolated perfused skeletal muscle preparation. Comparisons were made between erythrocytes subjected to a process of 'rejuvenation' (Rennie and Holloszy (1977), Biochem. J. 168, 161-170) and untreated erythrocytes (controls). (2) The use of rejuvenated erythrocytes had no significant effect on concentrations of muscle ATP, phosphocreatine and lactate, nor fractional rates of muscle protein synthesis. However, muscle water concentrations were reduced when compared to controls. (3) There was an influx of K+ from the plasma into rejuvenated erythrocytes. This was accompanied by a substantial loss (17%) of intramuscular K+. There was also loss of K+ from control preparations but this amounted to approx. 1% of muscle content. (4) Erythrocyte fragility was greater in the control perfusate (6%, haemolysis) when compared to the medium with rejuvenated cells (1%, haemolysis). As a consequence of either erythrocyte storage, rejuvenation or haemolysis, plasma concentrations of phosphate, magnesium, calcium and potassium were significantly different from starting values, by as much as 300% in both groups, and varied throughout the study. (5) It is concluded that the use of rejuvenated erythrocytes does not confer any advantage in unexercised perfused skeletal muscle preparations. However, both types of erythrocyte induce changes in perfusate composition relative to starting or in vivo profiles.

The effect of unilateral phrenicectomy on the rate of protein synthesis in rat diaphragm in vivo.

The fractional rate of protein synthesis (ks) in the denervated rat-diaphragm has been measured in vivo by the continuous amino acid infusion technique at 1, 3, 5 and 10 days after nerve section, and compared with the rate determined in normal rats. Similar rates of protein synthesis, 14% per day, were found for both the left and right hemidiaphragms in the control animals. In the denervated rats, the rates of protein synthesis in the contralateral control hemidiaphragms were significantly increased as soon as 1 day after nerve section. This is considered to be evidence of a compensatory synthesis in the control tissues. In the denervated hemidiaphragm, the rate of protein synthesis had doubled by the third day after nerve section, but by the fifth day had fallen slightly to a value some 50% greater than that of the controls, and remained at this level for a further 5 days. Based on these measured values of protein synthetic rate, calculated estimates have been made of the rate of protein degradation necessary to account for the reported (Turner, L.V. and Manchester, K.L. (1972) Biochem. J. 128, 789-801) changes in mass of the denervated tissue. During the first three days after nerve section, the rate constant for degradation increased to more than twice the normal rate for skeletal muscle, and remained at this value throughout the peak of the hypertrophy.

The effect of protein deprivation and starvation on the rate of protein synthesis in tissues of the rat.

1. The fractional rate of protein synthesis was measured in tissues of rats in vivo by continuous infusion of [14C]tyrosine. In growing animals proteins of liver and kidney were renewed at a rate greater than 50% per day, those in skeletal muscle, brain and heart at a rate between 13 and 23% per day. 2. Protein synthesis was also measured in liver, kidney, heart, brain and skeletal muscle of rats either given a protein-free diet for 21 days or starved for 2 days. During the first 2 days no clear differences between the effects of these two regimes could be detected. 3. Gastrocnemius muscle did not lose tissue protein till after 9 days without protein in the diet. The rate of protein synthesis was halved after 1 day and halved again after 21 days without protein. It was deduced that the rate of protein breakdown in muscle had declined also. 4. In liver the loss of protein was immediate without any apparent change in the fractional rate of protein synthesis. Between 2 and 21 days of dietary protein deprivation the liver lost protein slowly but the fractional rate of protein synthesis was increased. It is proposed that lack of protein in the diet also causes an increase in the rate of liver protein breakdown.

Influence of dietary protein intake on whole-body protein turnover in humans.

Methods for measuring rates of protein synthesis and degradation in the whole body of humans with isotopes of carbon and nitrogen are described and attention is drawn to their relative merits and drawbacks for studying the nutritional control of protein metabolism. A review of published work on dietary protein and protein metabolism leads to the conclusion that protein is the major dietary determinant of whole-body protein turnover rates, and that energy intake is comparatively unimportant. Dietary protein affects protein turnover at two levels: an immediate response to the intake of protein in meals and a longer-term adaptation after a change in protein intake. An increase in the level of dietary protein enhances the response to meals, which mainly consists of a decrease in the rate of protein degradation. The adaptation to higher protein intakes involves an increase in the basal (postabsorptive) rates of both synthesis and degradation. Suggestions for future investigation include more detailed studies of the acute and adaptive responses, to facilitate understanding of dietary protein requirements, and the effects of very-high-protein intakes with continued development of techniques for studying protein turnover in individual tissues in humans.

Albumin synthesis and bone collagen formation in human immunodeficiency virus-positive subjects: differential effects of growth hormone administration.

Loss of lean tissue often accompanies human immunodeficiency virus (HIV) infection. Exogenous human recombinant GH (hrGH) has been shown to be beneficial in reversing this wasting. However, catabolic effects of hrGH on muscle protein metabolism have also been reported. Therefore, the responsiveness of other GH-sensitive tissues, including bone formation and albumin synthesis, has been examined. Anabolic activity in bone, from serum levels of carboxy-terminal propeptide of type I collagen, was stimulated by 2 weeks of hrGH in controls (56 +/- 15%, P = 0.002), patients with asymptomatic HIV (24 +/- 10%, not significant), patients with AIDS (47 +/- 7%, P < 0.001), and patients with AIDS and > 10% weight loss (21 +/- 12%, P = 0.02). Albumin synthesis, determined from the incorporation of L-[2H5]phenylalanine, was increased in response to hrGH in controls (23 +/- 7%, P < 0.05), HIV+ subjects (39 +/- 16%, P < 0.05), and patients with AIDS (25 +/- 7%, P < 0.01). Patients with AIDS and weight loss, however, did not increase albumin synthesis (-0.6 +/- 12%) in response to hrGH. The results indicate variable anabolic responses to hrGH. Bone collagen synthesis remained sensitive to hrGH, whereas, the anabolic action of hrGH on the synthesis of albumin diminished with severity of disease. However unlike muscle protein synthesis, albumin synthesis was not depressed below basal levels by hrGH.

Diurnal pattern of protein and energy metabolism in man.

Rates of synthesis and breakdown of body protein and oxidation of leucine were measured in six obese subjects by constant intravenous infusion of (1 14C)leucine for 24-hr periods. During the night, when no food was given, the rate of whole body protein synthesis was 67% of the rate observed furing the day, when food was given hourly. By contrast the rate of body protein breakdown remained constant over the full 24 hr. This resulted in the immediate deposition of about 30% of the protein intake during the day, whereas the remaining 70% was immediately oxidized. At night the rate of protein oxidation fell to only 38% of its daytime value. The rate of oxygen consumption also decreased at this time so that the contributon of protein oxidation to total energy expenditure fell from 27% during the day to 13% at night. These changes reflect the normal, discontinuous pattern of food intake and the need during feeding to store protein in tissues for use in subsequent periods of fasting.

Whole-body protein turnover from leucine kinetics and the response to nutrition in human immunodeficiency virus infection.

Whole-body protein metabolism was investigated in human immunodeficiency virus (HIV) infection by primed constant infusion of L-[1-13C]leucine in 8 control and 22 HIV-infected subjects (8 stage II; 14 stage IV disease), in postabsorptive and fed states. Postabsorptive leucine flux was increased 25% in subjects with stage IV HiV infection vs that in control subjects (130 +/- 13 vs 103 +/- 10 mumol leucine.kg-1.h-1, P < 0.001); both leucine disposal by protein synthesis (111.6 +/- 12.1 vs 82.3 +/- 9.2, P < 0.001) and release by protein degradation (129.7 +/- 13.1 vs 103.4 +/- 10.2, P < 0.001) were increased. No difference in leucine balance or oxidation was found but fat oxidation was greater in subjects with HIV infection (61.1 +/- 13.0% of energy) than in control subjects (47.6 +/- 13.7% of energy, P < 0.025). Stage II subjects had intermediate values of leucine flux, not significantly different from those of control subjects. Provision of parenteral nutrition for 4 h increased leucine flux with a switch in leucine balance from net loss to net gain; this response was quantitatively similar in all groups. HIV infection increases whole-body protein turnover but does not quantitatively impair the acute anabolic response to intravenous nutrition.

Protein metabolism in the cancer patient.

The 'flooding' method has been widely used for measuring protein synthesis in animal tissues in vivo and in vitro, employing radioactively labelled amino acids, because it minimises errors in determining the specific radioactivity of the direct precursor of protein synthesis. This approach has now been modified for measuring protein synthesis rates in tumours and healthy tissues of humans by injection of the stable isotopic labels, [1(-13)C]leucine or [2H5]phenylalanine, followed by tissue sampling during surgery. Based on the observation that rates of protein synthesis correlate with changes in the expression of cell proliferation markers, we have suggested that changes in protein synthesis in tumours can be used as indices of changes in tumour growth. Measurements in colorectal cancer patients have shown that protein synthesis is stimulated 80% by feeding, suggesting that the tumour is not a pure parasite, but responds to exogenous nutrients. Moreover, when the composition of the amino acids given to the patient was changed from a balanced mixture to one supplemented with branched chain amino acids, the response of the tumour to feeding was significantly diminished, suggesting that tumour growth might be modulated by diet composition. Dietary supplements of arginine have been shown previously to inhibit tumour growth in animals, probably by activating the immune system. However, in breast cancer patients arginine stimulated tumour protein synthesis, suggesting that arginine might have separate stimulatory effects on the tumour and the immune system, the outcome depending on which effect predominates.

Acute metabolic acidosis decreases muscle protein synthesis but not albumin synthesis in humans.

Chronic metabolic acidosis induces negative nitrogen balance by either increased protein breakdown or decreased protein synthesis. Few data exist regarding effects of acute metabolic acidosis on protein synthesis. We investigated fractional synthesis rates (FSRs) of muscle protein and albumin, plasma concentrations of insulin-like growth factor-I (IGF-I), thyroid-stimulating hormone (TSH), and thyroid hormones (free thyroxin [fT(4)] and triiodothyronine [fT(3)]) in seven healthy human volunteers after a stable controlled metabolic period of 5 days and again 48 hours later after inducing metabolic acidosis by oral ammonium chloride intake (4.2 mmol/kg/d divided in six daily doses). Muscle and albumin FSRs were obtained by the [(2)H(5)ring]phenylalanine flooding technique. Ammonium chloride induced a significant decrease in pH (7.43 +/- 0.02 versus 7.32 +/- 0.04; P < 0.0001) and bicarbonate concentration (24.6 +/- 1.6 versus 16.0 +/- 2.7 mmol/L; P < 0.0001) within 48 hours. Nitrogen balance decreased significantly on the second day of acidosis. The FSR of muscle protein decreased (1.94 +/- 0.25 versus 1.30 +/- 0.39; P < 0.02), whereas the FSR of albumin remained constant. TSH levels increased significantly (1.1 +/- 0.5 versus 1.9 +/- 1.1 mU/L; P = 0.03), whereas IGF-I, fT(4), and fT(3) levels showed no significant change. We conclude that acute metabolic acidosis for 48 hours in humans induces a decrease in muscle protein synthesis, which contributes substantially to a negative nitrogen balance. In contrast to prolonged metabolic acidosis of 7 days, a short period of acidosis in the present study did not downregulate albumin synthesis.

Growth hormone together with glutamine-containing total parenteral nutrition maintains muscle glutamine levels and results in a less negative nitrogen balance after surgical trauma.

BACKGROUND: Muscle protein catabolism, reflected by a decrease in glutamine (GLN), a decrease in muscle protein synthesis, and a negative nitrogen balance can be reduced by either administration of GLN or growth hormone (GH). In this study, the effects of a combination of GH and GLH were studied. METHODS: Patients (n = 16) undergoing abdominal operation were given total parenteral nutrition (TPN) containing either GLN alone or GLN together with GH (GH/GLN) during 3 postoperative days. The amino acid concentration and protein synthesis in muscle tissue and the nitrogen balance were measured. RESULTS: GH/GLN reduced nitrogen losses compared with GLN alone (-5.8 +/- 1.4 g nitrogen versus -10.6 +/- 1.1 g nitrogen, P <.05). GH/GLN maintained muscle GLN at preoperative levels compared with a 47.5% +/- 6.3% decline in the GLN group. A similar decrease was seen in the fractional synthesis rate of muscle protein postoperatively in both groups. CONCLUSIONS: GH has an additive effect given together with GLN on muscle amino acid metabolism, preventing the decrease in the GLN concentration in skeletal muscle and diminishing the loss of whole body nitrogen. However, the improvements in muscle amino acid concentrations and nitrogen loss were not associated with differences between the groups in muscle protein synthesis postoperatively.

Growth hormone does not affect albumin synthesis in the critically ill.

OBJECTIVE: To study the effect of growth hormone (GH) on albumin synthesis in critically ill patients. DESIGN: Prospective randomized controlled study. SETTING: Two intensive care units, university hospital and county hospital, respectively. PATIENTS: Twenty-two critically ill patients in the intensive care unit. INTERVENTIONS: Albumin synthesis was measured twice in each patient, with a 5-day interval. The patients in the control group (n = 11) received standard intensive care unit (ICU) treatment between measurements, whereas those in the GH group (n = 11) also received 0.3 U/kg daily of human recombinant GH. MEASUREMENTS AND RESULTS: Albumin synthesis was measured by labeling with L-[2H5]phenylalanine. In the control group, the fractional synthesis rate (FSR) of albumin was 16.3+/-4.1%/day (mean and SD) in the first measurement and 15.7+/-4.2%/day 5 days later (NS), whereas in the GH group the corresponding values were 17.0+/-4.7%/day and 16.7+/-5.5%/day (NS). The calculated absolute synthesis rates of albumin, based on FSR and intravascular albumin mass, also showed no effect of GH. CONCLUSION: Albumin synthesis rates were consistently higher in the two groups of critically ill patients than previously reported values in healthy subjects. However, GH treatment for 5 days neither stimulated nor inhibited albumin synthesis rates in these critically ill patients.

A combined stress hormone infusion decreases in vivo protein synthesis in human T lymphocytes in healthy volunteers.

In vivo protein synthesis decreases in mononuclear cells following a combined stress hormone infusion given to healthy volunteers as a human trauma model. Here, the purpose was to further investigate this finding and to measure in vivo protein synthesis in isolated T lymphocytes. Furthermore, the effects of stress hormones on the lymphocyte subpopulations and mononuclear cells, characterized by flow cytometry and phytohemagglutinin (PHA)-induced and unstimulated proliferative responses in vitro, were elucidated. Healthy volunteers (n = 16) were randomized into 2 groups to receive either a stress hormone or a saline infusion for 6 hours. In vivo protein synthesis was studied before and after the treatment by measuring the incorporation of stable isotopically-labeled phenylalanine into lymphocyte and mononuclear cell proteins. Protein synthesis decreased after stress hormone infusion in both cell populations: in T lymphocytes from 13.0% +/- 0.7%/d (mean +/- SD) to 8.6% +/- 2.1%/d (P <.01) and in mononuclear cells from 13.3% +/- 1.2%/d to 6.3 +/- 2.0%/d (P <.001). No change in proliferative responsiveness in vitro was observed. The stress hormone infusion produced a decrease in the percentage of T helper CD3/CD4 from 41% to 18% (P <.001), T cytotoxic CD3/CD8 from 27% to 15% (P <.001), as well as total T CD3 cells from 69% to 35% (P <.001). There was an increase in the percentage of natural killer (NK) cells CD16/CD56 from 17% to 55% (P <.001). Determination of phenotypes expressed on activated T lymphocytes showed that CD3/HLA-DR was unchanged and CD3/CD25 decreased from 14% to 7% (P <.01) in the stress hormone group. The study showed that the decrease of in vivo protein synthesis was 34% in T lymphocytes as compared with 53% in mononuclear cells, when determined immediately after a 6-hour stress hormone infusion. This change was associated with a pronounced decrease in all lymphocyte subpopulations, except for the NK cells, which increased substantially.

Protein synthesis rates of skeletal muscle, lymphocytes, and albumin with stress hormone infusion in healthy man.

The rate of protein synthesis was assessed in muscle, lymphocytes, and albumin in healthy volunteers administered an infusion of 6.0 micrograms cortisol +3.0 ng glucagon +0.5 nmol epinephrine min-1.kg-1. Protein synthesis in muscle tissue was not sensitive to the immediate effects of hormone infusion, but decreased significantly by 18 hours after the infusion had ceased (1.77% +/- 0.12% per day v 1.29% +/- 0.10%, P < .05). The rate of protein synthesis in lymphocytes was acutely sensitive to the effect of the hormone infusion, decreasing from 7.15% +/- 1.02% per day to 2.47% +/- 0.5% (P < .05). However, measurements made 18 hours after the end of the hormone infusion indicated that lymphocyte protein synthesis returned to the preinfusion rates. The rate of albumin synthesis was unaltered during infusion of the stress hormones, but was significantly increased when measured 18 hours after ending the hormone infusion (6.84% +/- 0.43% per day v 7.99% +/- 0.45%, P < .05). Thus, tissues respond differently to stress hormone infusion, demonstrating the importance of studying multiple organ systems when assessing the regulation of protein metabolism.

The role of degradation in the acute control of protein balance in adult man: failure of feeding to stimulate protein synthesis as assessed by L-[1-13C]leucin infusion.

The effect of feeding on whole-body protein turnover was measured in six healthy volunteers using the essential amino acid, L-[1-13C]leucine, as a tracer for protein metabolism. Varied lengths of periods of feeding and isotope infusion produced different apparent responses to feeding. When parameters of protein turnover were estimated from 8-hour infusions, the change from post-absorptive in the first four hours to mixed feeding during the final four hours was found to produce positive leucine balance by decreasing degradation from 89.5 +/- 5.0 to 31.7 +/- 7.3 mumol leucine/kg/h (P less than .001), with no apparent change in synthesis. By contrast, when tracer was infused for 24 hours with 12 hours of feeding followed by 12 hours of fasting, the estimate of protein synthesis during feeding was 35% higher than during fasting (P less than .01). However, when tracer infusion during the 12-hour feeding/12-hour fasting protocol was limited to the last four hours of each nutritional period, the estimates of fed and fasted protein synthesis showed no significant difference, 71.3 +/- 6.5 and 66.2 +/- 5.6 respectively, while the calculated rate of protein degradation was 43% lower during feeding (P less than .002). As relatively higher levels of enrichment in plasma leucine were detected in comparable nutritional states following longer infusions, the possibility of significant recycling of label was investigated. Residual tracer was still detectable in both breath and plasma 12 hours after cessation of a 12-hour tracer infusion, supporting the conclusion that significant errors in estimates of protein turnover due to recycling of label arise with prolonged infusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Protein synthesis in adult skeletal muscle after tenotomy: responses to fasting and insulin infusion.

Muscle growth was established in specific muscles in the hindlimb of adult female rats by tenotomy of the gastrocnemius muscle. Seven days after surgery there was an increase in the wet weight of the soleus (Sol) and plantaris (P) muscles and a decrease in that of the gastrocnemius (G) muscle from the tenotomized limb compared with the respective control muscles from the contralateral limb from the same animal. In all three muscles there was a significant increase in the fractional rate of protein synthesis (ks) in the muscles from the tenotomized limb above the rate of the respective control muscles. In contrast, the extensor digitorum longus (EDL) muscle showed no change in wet weight or ks 7 days after tenotomy of G. Fasting for 12 or 36 h had no significant effect on ks in G, P, or Sol muscles from either the control or tenotomized limbs. In EDL from the control limb, both fasting periods resulted in a significant decrease in ks, although this effect was not seen in the EDL from the tenotomized limbs of the same animals. A subsequent 30-min insulin infusion was similarly ineffectual in G, P, and Sol, with its only effect evident in the EDL from the control limb, where it was sufficient to reverse the decreased ks resulting from the fasting, even though after 36 h fasting the reversal was only partial.