Incidence of acute rheumatic fever: a persistent dilemma.
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Child↗
Biomedical subjects
R R Wolfe
Publications and source records attributed to R R Wolfe.
Inhibition of muscle glutamine formation in hypercatabolic patients.
Glutamine is synthesized primarily in skeletal muscle, and enables transfer of nitrogen to the liver, as well as serving other functions. There is increasing evidence for beneficial clinical effects of glutamine supplementation in critically ill patients. However, the response of endogenous glutamine formation to severe stress is poorly understood. The rates of net protein balance, leucine oxidative decarboxylation, and alanine and glutamine synthesis de novo were determined in leg skeletal muscle of 20 severely burned patients and 19 normal controls in the post-absorptive state. Patients were studied at 14+/-5 days post-burn, and their mean burn size was 66+/-18% of total body surface area. Methods were based on the leg arteriovenous balance technique in combination with biopsies of the vastus lateralis muscle. In the post-absorptive state, patients with severe burns, as compared with healthy control subjects, exhibited accelerated muscle loss (+150%) (i.e. proteolysis minus synthesis) and leucine oxidative decarboxylation (+117%), and depletion of the intramuscular free glutamine pool (-63%). The average rate of glutamine synthesis de novo was decreased by 48%, whereas net alanine synthesis de novo was increased by 174%, in skeletal muscle of burned patients. In conclusion, in severely hypercatabolic burned patients, muscle glutamine formation was suppressed, whereas alanine was the major vehicle for inter-organ nitrogen transport. These changes account for a decreased glutamine availability during prolonged severe stress.
Adult↗
Nonessential amino acids are not necessary to stimulate net muscle protein synthesis in healthy volunteers.
The present study was performed to test the hypothesis that orally administered essential amino acids, in combination with carbohydrate, will stimulate net muscle protein synthesis in resting human muscle in vivo. Four volunteers ingested 500 mL of a solution containing 13.4 g of essential amino acids and 35 g sucrose (EAA). Blood samples were taken from femoral arterial and venous catheters over a 2-hour period following the ingestion of EAA to measure arteriovenous concentrations of amino acids across the muscle. Two muscle biopsies were taken during the study, one before administration of the drink and one approximately 2 hours after consumption of EAA. Serum insulin increased from normal physiologic levels at baseline (9.2 +/- 0.8 microU/mL) and peaked (48 +/- 7.1 microU/mL) 30 minutes after EAA ingestion. Arterial essential amino acid concentrations increased approximately 100 to 400% above basal levels between 10 and 30 minutes following drink ingestion. Net nitrogen (N) balance changed from negative (-495 +/- 128 nmol/mL) prior to consumption of EAA to a peak positive value (416 +/- 140 nmol/mL) within 10 minutes of ingestion of the drink. EAA resulted in an estimated positive net N uptake of 307.3 mg N above basal levels over the 2-hour period. Muscle amino acid concentrations were similar prior to and 2 hours following ingestion of EAA. We conclude that ingestion of a solution composed of carbohydrates to stimulate insulin release and a small amount of essential amino acids to increase amino acid availability for protein synthesis is an effective stimulator of muscle protein anabolism.
Journal Article↗
Regional disposal of intravenously infused glucose during prolonged hyperglycemia-hyperinsulinemia.
We measured splanchnic and leg glucose uptake during prolonged (i.e., 15 hours), moderate hyperglycemia-hyperinsulinemia (clamp). Plasma free fatty acid (FFA) concentration was maintained at basal concentration during the clamp via infusion of exogenous lipids and heparin in healthy volunteers to create a metabolic profile similar to glucose intolerance (i.e., hyperglycemia-hyperinsulinemia with elevated FFA concentration). During the clamp, glucose was infused at an average rate of 49 +/- 4 micromol/kg/min, which resulted in a plasma glucose concentration of 8.8 +/- 0.5 mmol/L compared with a concentration of 4.4 +/- 0.2 mmol/L in the basal state (P < 0.05). Insulin concentration increased from 5.5 +/- 1.1 microU/mL (basal) to 31.3 +/- 12.7 microU/mL (clamp; P < 0.05), whereas plasma FFA concentration was similar in the two conditions (3.9 +/- 0.5 mmol/L and 4.1 +/- 0.5 mmol/L, basal and clamp, respectively). Glucose balance across the splanchnic region switched from net release (-5.8 +/- 0.7 micromol/kg/min) in the basal state to net uptake in the clamp (19.8 +/- 3.7 micromol/kg/min; P < 0.05) and accounted for approximately 40% of the infused glucose. Glucose uptake across the leg was 0.7 +/- 0.2 micromol/kg/min (basal) and 5.5 +/- 2.2 micromol/kg/min (clamp; P < 0.05). In summary, tissues in the splanchnic region (i.e., liver) are important for disposal of intravenously infused glucose during prolonged, moderate hyperglycemia-hyperinsulinemia. Accelerated hepatic glucose uptake may disrupt normal liver metabolism, with potentially dangerous consequences for the patient. Measures to control systemic glucose concentration may be necessary to prevent excessive glucose disposal in the liver.
Journal Article↗
Physical exercise as a modulator of adaptation to low and high carbohydrate and low and high fat intakes.
Quantification of the metabolic response aids in ascertaining the nature and extent of the energy requirements imposed by exercise. During high intensity exercise, virtually all of the energy is supplied by the net oxidation of glycogen while fat oxidation plays a more prominent role during lower intensity exercise. Therefore, the lower limit of carbohydrate required above resting needs is equal to the portion of the total energy cost derived from carbohydrate sources. There is no upper limit of additional carbohydrate intake that could be eaten to satisfy the extra caloric requirement since carbohydrate intake will restore any endogenous energy stores that were used during exercise, regardless of the intensity of exercise. The recommendation of a high carbohydrate intake to provide caloric balance in exercising individuals is supported by the observation that exercise performance at high intensity is improved by a high carbohydrate diet, and exercise performance at low intensity is relatively insensitive to the source of the caloric intake. Limited dietary studies are consistent with predictions based on the metabolic response. At exercise intensities below 65% VO2 max, the percent fat and carbohydrate in the diet makes little difference on exercise performance, provided adequate time is allowed to adapt to a high-fat diet. On the other hand, exercise ability during high-intensity exercise is significantly limited by a high-fat diet. A consideration of importance beyond the aspect of energy balance is the anabolic effect of insulin on muscle protein synthesis after exercise. Provision of carbohydrate after exercise is likely to stimulate muscle protein synthesis to a greater extent than a corresponding amount of fat. Dietary fats may offer practical advantages to the athlete but if fats are consumed at the expense of carbohydrate intake, many established benefits of high carbohydrate intake in terms of performance may be sacrified.
Adaptation, Physiological↗
Sepsis as a modulator of adaptation to low and high carbohydrate and low and high fat intakes.
Catabolism of lean body mass (particularly muscle) occurs in sepsis and other forms of critical illness despite apparently adequate nutritional support. The determination of the optimal balance of carbohydrate and fat intake in this circumstance should be based on the resulting effect on the maintenance of lean body mass, and the nature and extent of any side effects. The general stress response involves a disruption in normal glucoregulation, in that hepatic glucose production is accelerated and the normal blood glucose lowering action of insulin is diminished. Nonetheless, the capacity to oxidize glucose once inside the cells is not impaired. Lipolysis, or the breakdown of peripheral triglycerides to free fatty acids (FFA) and glycerol, is accelerated in critical illness, to a greater extent than fat oxidation. Provision of exogenous fat maintains fat stores, but has minimal effect on the direct oxidation of plasma FFA. From the results of oxidation studies, it seems that about 5 mg kg x min of glucose can be readily oxidized, and the balance of energy will be supplied by the oxidation of fat, either endogenous or exogenous. However, an additional consideration in determining the optimal caloric substrate is that insulin is a potent anabolic hormone and stimulates muscle protein synthesis. Consequently, provision of exogenous insulin enhances retention of muscle. This procedure dictates that almost all non-protein calories be provided as carbohydrate to avoid hypoglycemia. Preliminary studies suggest this may be the optimal approach in critically ill patients. Glucose and fatty acids are the major energy substrates in the body. The oxidative metabolism of these substrates provides the ATP needed for physiological function, including protein synthesis. Over the past 20 y, development of new techniques in nutritional support have made it possible to provide large amounts of carbohydrate and fat to critically-ill patients, along with protein or amino acids. However, despite providing such patients with what should be more than adequate caloric and protein intake, critically ill patients lose lean body mass (Streat et al, 1987), largely because of persistent muscle catabolism (Sakurai et al, 1995). The general relation between energy substrate metabolism and maintenance of lean body mass has been recognized for many years (Calloway & Spector, 1954), so it is important to examine the alterations in energy substrate metabolism that occur in response to critical illness that may play a role in causing the persistent catabolism of muscle protein.
Adaptation, Physiological↗
A submaximal dose of insulin promotes net skeletal muscle protein synthesis in patients with severe burns.
OBJECTIVE: To investigate the hypothesis that a submaximal insulin dose reverses the net muscle catabolism associated with severe burns, and to determine its effects on amino acid kinetics. SUMMARY BACKGROUND DATA: The authors previously showed that a maximal dose of insulin administered to patients with severe burns promoted skeletal muscle glucose uptake and net protein synthesis. However, this treatment was associated with caloric overload resulting from the large quantities of exogenous glucose required to maintain euglycemia, and hypoglycemia was a potential problem. METHODS: Thirteen patients were studied after severe burn injury (>60% total body surface area). Patients were randomly treated by standard care (n = 5) or with exogenous insulin (n = 8). Data were derived from an arteriovenous model with primed-continuous infusions of stable isotopes and biopsies of the vastus lateralis muscle. RESULTS: Net amino acid balance was significantly improved with insulin treatment. Skeletal muscle protein synthesis was significantly greater in the group receiving insulin, whereas muscle protein breakdown was not different between the groups. This submaximal dose of insulin did not affect glucose or amino acid uptake or require a greater caloric intake to avoid hypoglycemia. CONCLUSIONS: Submaximal insulin can promote muscle anabolism without eliciting a hypoglycemic response.
Amino Acids↗
Muscle protein catabolism after severe burn: effects of IGF-1/IGFBP-3 treatment.
OBJECTIVE: To determine the effects of recombinant human insulin-like growth factor-1 (IGF-1) complexed with its principal binding protein, IGFBP-3, on skeletal muscle metabolism in severely burned children. SUMMARY BACKGROUND DATA: Severe burns are associated with a persistent hypermetabolic response characterized by hyperdynamic circulation and severe muscle catabolism and wasting. Previous studies showed that nutritional support and pharmacologic intervention with anabolic agents such as growth hormone and insulin abrogated muscle wasting and improved net protein synthesis in the severely burned. The use of these agents, however, has several adverse side effects. A new combination of IGF-1 and IGFBP-3 is now available for clinical study. METHODS: Twenty-nine severely burned children were prospectively studied before and after treatment with 0.5, 1, 2, or 4 mg/kg/day IGF-1/IGFBP-3 to determine net balance of protein across the leg, muscle protein fractional synthetic rates, and glucose metabolism. Another group was studied in a similar fashion without IGF-1/IGFBP-3 treatment as time controls. RESULTS: Seventeen of 29 children were catabolic before starting treatment. The infusion of 1.0 mg/kg/day IGF-1/IGFBP-3 increased serum IGF-1, which did not further increase with 2.0 and 4.0 mg/kg/day. IGF-1/IGFBP-3 treatment at 1 to 4 mg/ kg/day improved net protein balance and increased muscle protein fractional synthetic rates. This effect was more pronounced in catabolic children. IGF-1/IGFBP-3 did not affect glucose uptake across the leg or change substrate utilization. CONCLUSIONS: IGF-1/IGFBP-3 at doses of 1 to 4 mg/kg/day attenuates catabolism in catabolic burned children with negligible clinical side effects.
Burns↗
Anabolic effects of insulin-like growth factor in combination with insulin-like growth factor binding protein-3 in severely burned adults.
BACKGROUND: The purpose of this study was to determine the anabolic effects of recombinant human insulin-like growth factor-I (rhIGF-1) complexed with its principal binding protein IGF-1 binding protein-3 (IGFBP-3) in severely burned adults. METHODS: Ten burned adults were studied consecutively after receiving saline (pretreatment), then rhIGF-1/IGFBP-3 (treatment) for 5 days. Doses were 1, 2, and 4 mg/kg per day. Glucose, electrolytes, hormones, and leg muscle protein metabolism were determined. Nine other studies were performed on similarly injured adults at comparable times to the treatment studies to control for time effects. RESULTS: Serum IGF-1 and IGFBP-3 levels increased with all doses, but no incremental increases were found. Leg protein balance improved with rhIGF-1/IGFBP-3, which was associated with an increase in muscle protein fractional synthetic rate. These effects were independent of time. All patients were euglycemic without electrolyte imbalances. CONCLUSION: Net protein synthesis in the isolated leg of severely burned adults improved with rhIGF-1/IGFBP-3 without development of glucose abnormalities.
Adult↗
Regulation of fatty acid oxidation in skeletal muscle.
Researchers using animals are beginning to elucidate the control of fatty acid metabolism in muscle at the molecular and enzymatic level. This review examines the physiological data that has been collected from human subjects in the context of the proposed control mechanisms. A number of factors, including the availability of free fatty acids and the abundance of fatty acid transporters, may influence the rate of muscle fatty acid oxidation. However, the predominant point of control appears to be the rate at which fatty acyl-coenzyme A is transported into the mitochondria by the carnitine palmitoyl transferase system. In turn, evidence suggests that the intracellular concentration of malonyl-coenzyme A in muscle is an important regulator of carnitine palmitoyl transferase-I activity. Malonyl-coenzyme A is increased by glucose, which is likely the mechanism whereby glucose intake suppresses the transfer of fatty acids into the mitochondria for subsequent oxidation. In contrast, malonyl-coenzyme A levels decrease during exercise, which enables increased fatty acid oxidation. However, for any given carnitine palmitoyl transferase-I activity, there may be an effect of free fatty acid availability on fatty acid oxidation, particularly at low levels of free fatty acids. Nonetheless, the rate of glucose or glycogen metabolism is probably the primary regulator of the balance between glucose and fatty acid oxidation in muscle.
Animals↗
Resistance training reduces the acute exercise-induced increase in muscle protein turnover.
We examined the effect of resistance training on the response of mixed muscle protein fractional synthesis (FSR) and breakdown rates (FBR) by use of primed constant infusions of [2H5]phenylalanine and [15N]phenylalanine, respectively, to an isolated bout of pleiometric resistance exercise. Trained subjects, who were performing regular resistance exercise (trained, T; n = 6), were compared with sedentary, untrained controls (untrained, UT; n = 6). The exercise test consisted of 10 sets (8 repetitions per set) of single-leg knee flexion (i.e., pleiometric muscle contraction during lowering) at 120% of the subjects' predetermined single-leg 1 repetition maximum. Subjects exercised one leg while their contralateral leg acted as a nonexercised (resting) control. Exercise resulted in an increase, above resting, in mixed muscle FSR in both groups (UT: rest, 0.036 +/- 0.002; exercise, 0.0802 +/- 0.01; T: rest, 0.045 +/- 0.004; exercise, 0.067 +/- 0.01; all values in %/h; P < 0.01). In addition, exercise resulted in an increase in mixed muscle FBR of 37 +/- 5% (rest, 0.076 +/- 0.005; exercise, 0.105 +/- 0.01; all values in %/h; P < 0.01) in the UT group but did not significantly affect FBR in the T group. The resulting muscle net balance (FSR - FBR) was negative throughout the protocol (P < 0.05) but was increased in the exercised leg in both groups (P < 0.05). We conclude that pleiometric muscle contractions induce an increase in mixed muscle protein synthetic rate within 4 h of completion of an exercise bout but that resistance training attenuates this increase. A single bout of pleiometric muscle contractions also increased the FBR of mixed muscle protein in UT but not in T subjects.
Adult↗
Effect of hyperglycemia-hyperinsulinemia on whole body and regional fatty acid metabolism.
The effects of combined hyperglycemia-hyperinsulinemia on whole body, splanchnic, and leg fatty acid metabolism were determined in five volunteers. Catheters were placed in a femoral artery and vein and a hepatic vein. U-13C-labeled fatty acids were infused, once in the basal state and, on a different occasion, during infusion of dextrose (clamp; arterial glucose 8.8 +/- 0.5 mmol/l). Lipids and heparin were infused together with the dextrose to maintain plasma fatty acid concentrations at basal levels. Fatty acid availability in plasma and fatty acid uptake across the splanchnic region and the leg were similar during the basal and clamp experiments. Dextrose infusion decreased fatty acid oxidation by 51.8% (whole body), 47.4% (splanchnic), and 64.3% (leg). Similarly, the percent fatty acid uptake oxidized decreased at the whole body level (53 to 29%), across the splanchnic region (30 to 13%), and in the leg (48 to 22%) during the clamp. We conclude that, in healthy men, combined hyperglycemia-hyperinsulinemia inhibits fatty acid oxidation to a similar extent at the whole body level, across the leg, and across the splanchnic region, even when fatty acid availability is constant.
Adult↗
Postexercise net protein synthesis in human muscle from orally administered amino acids.
We examined the response of net muscle protein synthesis to ingestion of amino acids after a bout of resistance exercise. A primed, constant infusion of L-[ring-2H5]phenylalanine was used to measure net muscle protein balance in three male and three female volunteers on three occasions. Subjects consumed in random order 1 liter of 1) a mixed amino acid (40 g) solution (MAA), 2) an essential amino acid (40 g) solution (EAA), and 3) a placebo solution (PLA). Arterial amino acid concentrations increased approximately 150-640% above baseline during ingestion of MAA and EAA. Net muscle protein balance was significantly increased from negative during PLA ingestion (-50 +/- 23 nmol. min-1. 100 ml leg volume-1) to positive during MAA ingestion (17 +/- 13 nmol. min-1. 100 ml leg volume-1) and EAA (29 +/- 14 nmol. min-1. 100 ml leg volume-1; P < 0.05). Because net balance was similar for MAA and EAA, it does not appear necessary to include nonessential amino acids in a formulation designed to elicit an anabolic response from muscle after exercise. We concluded that ingestion of oral essential amino acids results in a change from net muscle protein degradation to net muscle protein synthesis after heavy resistance exercise in humans similar to that seen when the amino acids were infused.
Administration, Oral↗
Insulin but not growth hormone stimulates protein anabolism in skin wound and muscle.
We have measured protein kinetics in the scalded skin and normal muscle in anesthetized rabbits. On the 7th day after ear scald, L-[ring-13C6]phenylalanine was infused as a tracer, and the ear and hindlimb were used as arteriovenous units to reflect skin and muscle protein kinetics. Insulin was infused at 0.6 or 2.3-3.4 mU. kg-1. min-1 in the low-dose and high-dose insulin groups. In the growth hormone group, recombinant human growth hormone was administered at 2 mg. kg-1. day-1 after the ear was scalded. The results were compared with a control group in which the ear was scalded but otherwise was not treated. In the control group, net protein loss in the scalded skin and muscle was 23.1 +/- 21.4 and 3.9 +/- 1.5 micromol. 100 g-1. h-1, respectively. Insulin infusion at either high or low dose reduced net protein loss to near zero by inhibiting proteolysis. In contrast, growth hormone treatment had no anabolic effect on either tissue. In conclusion, insulin but not growth hormone has an anabolic effect on scalded skin and normal muscle; low-dose insulin is as effective in achieving an anabolic effect on both tissues, with less hypoglycemic response than high-dose insulin.
Animals↗
Lung surfactant kinetics in conscious pigs.
The primary goal of this study was to determine the contributions of plasma free fatty acids (FFA) and de novo synthesized fatty acids (FA) to lung surfactant phosphatidylcholine (PC) synthesis. A new stable isotope tracer model was developed in which [1, 2-(13)C(2)]acetate and uniformly labeled [U-(13)C(16)]palmitate were infused in nine normal overnight fasted pigs to quantify surfactant kinetics in the basal state and during low-dose glucose infusion (2 mg. kg(-1). min(-1)). There was no effect of glucose; therefore, all data were pooled. The surfactant PC-bound palmitate incorporation rate from plasma palmitate was 20.9 +/- 1.9 nmol palmitate. h(-1). g wet lung(-1), compared with the rate of 2.1 +/- 0.3 nmol palmitate. h(-1). g wet lung(-1) from de novo synthesized palmitate. The PC-bound palmitate secretion rate from the lamellar body pool to the alveolar surface pool was 239 +/- 26 nmol palmitate. h(-1). g wet lung(-1). Approximately 90% of the secreted PC recycled back to the lamellar bodies for reutilization. We conclude that plasma is the primary contributor of FA for surfactant PC synthesis under the conditions of this experiment.
Animals↗
Oral amino acids stimulate muscle protein anabolism in the elderly despite higher first-pass splanchnic extraction.
Muscle protein synthesis and breakdown and amino acid transport were measured in 7 healthy young (30 +/- 2 yr) and 8 healthy elderly (71 +/- 2 yr) volunteers in the postabsorptive state and during the oral administration of an amino acid mixture with L-[ring-(2)H(5)]phenylalanine infusion, femoral artery and vein catheterization, and muscle biopsies. Phenylalanine first-pass splanchnic extraction was measured by adding L-[ring-(13)C(6)]phenylalanine to the mixture. In the postabsorptive state, no differences in muscle amino acid kinetics were detected between young and elderly volunteers. Phenylalanine first-pass splanchnic extraction was significantly higher in the elderly (P < 0. 003) during ingestion of amino acids, but the delivery to the leg increased to the same extent in both groups. Phenylalanine transport into the muscle, muscle protein synthesis, and net balance increased significantly (P < 0.01) and similarly in both the young and the elderly. We conclude that, despite an increased splanchnic first-pass extraction, muscle protein anabolism can be stimulated by oral amino acids in the elderly as well as in the young.
Administration, Oral↗
Assessment of methods for improving tracer estimation of non-steady-state rate of appearance.
The most common approach for estimating substrate rate of appearance (R(a)) is use of the single-pool model first proposed by R. W. Steele, J. S. Wall, R. C. DeBodo, and N. Altszuler. (Am. J. Physiol. 187: 15-24, 1956). To overcome the model error during highly non-steady-state conditions due to the assumption of a constant volume of distribution (V), two strategies have been proposed: 1) use of a variable tracer infusion rate to minimize tracer-to-tracee ratio (TTR) variations (fixed-volume approach) or 2) use of two tracers of the same substrate with one infused at a constant rate and the other at a variable rate (variable-volume approach or approach of T. Issekutz, R. Issekutz, and D. Elahi. Can. J. Physiol. Pharmacol. 52: 215-224, 1974). The goal of this study was to compare the results of these two strategies for the analysis of the kinetics of glycerol and glucose under the non-steady-state condition created by a constant infusion of epinephrine (50 ng. kg(-1). min(-1)) with the traditional approach of Steele et al., which uses a constant infusion and fixed volume. The results showed that for glucose and glycerol the estimates of R(a) obtained with the constant and the variable tracer infusion rate and the equation of Steele et al. were comparable. The variable tracer infusion approach was less sensitive to the choice of V in estimating R(a) for glycerol and glucose, although the advantage of changing the tracer infusion rate was greater for glucose than for glycerol. The model of Issekutz et al. showed instability when the ratio TTR(1)/TTR(2) approaches a constant value, and the model is more sensitive to measurement error than the constant-volume model for glucose and glycerol. We conclude that the one-tracer constant-infusion technique is sufficient in most cases for glycerol, whereas the one-tracer variable-infusion technique is preferable for glucose. Reasonable values for glucose R(a) can be obtained with the constant-infusion technique if V = 145 ml/kg.
Adult↗
Inactivity amplifies the catabolic response of skeletal muscle to cortisol.
Severe injury or trauma is accompanied by both hypercortisolemia and prolonged inactivity or bed rest (BR). Trauma and BR alone each result in a loss of muscle nitrogen, albeit through different metabolic alterations. Although BR alone can result in a 2-3% loss of lean body mass, the effects of severe trauma can be 2- to 3-fold greater. We investigated the combined effects of hypercortisolemia and prolonged inactivity on muscle protein metabolism in healthy volunteers. Six males were studied before and after 14 days of strict BR using a model based on arteriovenous sampling and muscle biopsy. Fractional synthesis and breakdown rates of skeletal muscle protein were also directly calculated. Each assessment of protein metabolism was conducted during a 12-h infusion of hydrocortisone sodium succinate (120 microg/kg x h), resulting in blood cortisol concentrations that mimic severe injury (approximately 31 microg/dL). After 14 days of strict BR, hypercortisolemia increased phenylalanine efflux from muscle by 3-fold (P < 0.05). The augmented negative amino acid balance was the result of an increased muscle protein breakdown (P < 0.05) without a concomitant change in muscle protein synthesis. Muscle efflux of glutamine and alanine increased significantly after bed rest due to a significant increase in de novo synthesis (P < 0.05). Thus, inactivity sensitizes skeletal muscle to the catabolic effects of hypercortisolemia. Furthermore, these effects on healthy volunteers are analogous to those seen after severe injury.
Adult↗