Insulin-Like Growth Factor-1 Lowers Protein Oxidation in Patients with Thermal Injury
William G. CioffiDennis C. GoreLoring W. RueGretchen J. CarrougherHans-Peter GulerWilliam F. McManusBasil A. Pruitt
136
Citation
42
Reference
10
Related Paper
Citation Trend
Abstract:
The effect of insulin-like growth factor-1 (IGF-1) on energy expenditure and protein and glucose metabolism in a group of patients with thermal injury was determined.Accelerated protein catabolism is a constant feature of the hypermetabolic response to thermal injury. Insulin-like growth factor-1 has been reported to minimize protein catabolism and normalize energy expenditure in animal models of thermal injury.To determine the efficacy of IGF-1 in human burn patients, resting energy expenditure (metabolic cart), whole body protein kinetics (N15 Lysine), and glucose disposal (glucose tolerance test) were assessed in eight burn patients before and after a 3-day infusion of IGF-1 (20 micrograms/kg/hr). All patients were fluid-resuscitated uneventfully and were without obvious infection at the time of study. Enteral nutrition was administered at a constant rate before and during the IGF-1 infusion.Resting energy expenditure was not altered by IGF-1 (40.3 +/- 2.2 vs. 39.1 +/- 2.3 kcal/kg/day). However, glucose uptake was promoted, and protein oxidation decreased significantly (0.118 +/- 0.029 vs. 0.087 +/- 0.021 g/kg/d, p < 0.05) by IGF-1. In addition, insulin secretion, in response to a glucose challenge, was blunted.Insulin-like growth factor-1 therapy has a beneficial effect in preserving lean body mass during severe stress conditions by minimizing the flux of amino acids toward oxidation.Keywords:
Resting energy expenditure
Catabolism
Hypermetabolism
Protein turnover
Enteral administration
Protein metabolism
Carbohydrate Metabolism
Summary: Protein turnover was studied in eight premature infants of conceptual age 26-37 weeks. A stochastic model based upon [15N]urea or [15N]ammonia excretion following a single injection of [15N]glycine was used to estimate rates of whole body protein synthesis and catabolism. The urinary 3-methylhistidine/creatinine ratio was determined to differentiate skeletal muscle protein breakdown from total protein catabolism. The rates of whole body protein synthesis ranged from 5.2 to 13.2 g·kg−1·day−1 and protein catabolism ranged from 4.1 to 12.4 g·kg−1·day−1. Linear regression analyses of conceptual age versus (a) whole body nitrogen flux, (b) protein synthesis, and (c) protein catabolism showed significant inverse relationships. A similar relationship obtained between conceptual age and the urine 3-methylhistidine/creatinine ratio. Muscle protein breakdown did not vary with conceptual age, but the fraction of whole body protein breakdown derived from muscle protein breakdown increased significantly with advancing maturation. The ratio net tissue protein gain/total body protein synthesis increased significantly with increasing body weight. Net tissue protein gain appeared to be directly related to protein and caloric intake. The ratio of the rate of whole body protein synthesis and protein intake was greatest in the youngest infants and declined with maturation. A similar relationship was not found between the ratio of protein synthesis and caloric intake and the degree of maturity. More than 90% of nitrogen entering the metabolic pool was used for protein synthesis and more than 50% of calories administered were similarly utilized. We conclude that: (a) protein turnover in premature infants is far more rapid than in term infants, children, or adults and is inversely related to conceptual age; (b) muscle protein turnover constitutes a greater fraction of overall turnover with advancing maturity; (c) energy and protein intake affect net tissue protein gain significantly in rapidly growing infants; and (d) the efficiency of protein synthesis as a function of protein intake is higher in the most immature infants.
Catabolism
Protein turnover
Protein metabolism
Nitrogen balance
Cite
Citations (33)
Muscle protein turnover and amino acid (AA) exchange were studied in 4 patients with chronic renal failure (CRF) and in 5 controls in the postabsorptive state by using the forearm perfusion method together with the systemic infusion of 3H-Phe. In CRF patients muscle protein breakdown is increased and is associated with a parallel increase in protein synthesis. Protein breakdown is inversely related to arterial bicarbonate. Net proteolysis is unchanged. The release of total AA, glutamine and alanine is not different from controls, whereas the release of valine and leucine is reduced and serine uptake tends to be decreased. In conclusion, in postabsorptive patients with CRF, well before the uremic stage, an increased protein breakdown associated with metabolic acidosis takes place; net proteolysis is unaffected. Alterations in BCAA metabolism suggest the occurrence of increased BCAA degradation proceeding beyond the transamination step.
Protein turnover
Proteolysis
Protein metabolism
Protein Degradation
Transamination
Bicarbonate
Alanine
Cite
Citations (13)
Resting energy expenditure
Protein turnover
Hypermetabolism
Catabolism
Protein metabolism
Cite
Citations (56)
Protein turnover
Protein metabolism
Nitrogen balance
Catabolism
Protein Degradation
Cite
Citations (60)
Protein metabolism
Catabolism
Protein turnover
Muscle protein
Nitrogen balance
Protein Degradation
Cite
Citations (81)
Our studies have focused on the regulation of whole body and skeletal muscle protein metabolism in premature infants. Net deposition of protein is the result of a positive balance between protein synthesis and breakdown. To measure protein metabolism we have employed end-product studies with [ 15 N]glycine and 13 [C]leucine. Myofibrillar protein degradation was estimated by measuring the excretion of N-t-methylhistidine in urine. Energy expenditure and substrate utilization were also measured. Premature infants have high rates of protein synthesis (12 g∙kg −1 ∙d −1 ), twice those measured in children and four times those found in adults. Intrauterine malnourished babies have increased rates of protein turnover. Very low birth weight infants (< 1500 g) have higher myofibrillar protein turnover than larger babies. Intravenous feeding decreases whole body protein turnover, and we estimate visceral protein synthesis to be approximately 4 g∙kg −1 ∙d −1 . Suboptimal energy intake worsens nitrogen utilization by reducing the reutilization of endogenous amino acids for protein synthesis. We have also examined the effects of varying the source of nonprotein energy (i.e., glucose only versus glucose plus lipid) at requirement levels and have shown there is no effect on protein metabolism. Recent improvements in technology have opened the way to detailed study of individual amino acid metabolism in neonates in the future.
Protein turnover
Protein metabolism
Nitrogen balance
Protein Degradation
Cite
Citations (13)
Hypermetabolism
Catabolism
Resting energy expenditure
Body surface area
Cite
Citations (515)
Cite
Citations (22)
Protein turnover
Catabolism
Nitrogen balance
Protein metabolism
Cite
Citations (131)
Convalescence
Protein turnover
Protein metabolism
Catabolism
Protein Degradation
Cite
Citations (175)