Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Postoperative Muscle and Substrate Metabolism

This study explored if a combined supplementation of GH and IGF-1 had an additive effect on whole body nitrogen economy, energy, substrate and skeletal muscle metabolism following surgical trauma. Patients were randomized to controls (C;n=10), to GH (0.15 IU/kg/injection) (GH;n=7) or GH combined with IGF-1 (40 μg/kg/injection) subcutaneously twice a day (GH-IGF-1;n=9) together with standardized parenteral nutrition. Muscle amino acids, glutathione and the ribosomal pattern reflecting protein synthesis, and nitrogen balance were measured. GH- and GH-IGF-1 groups showed lower urea and higher plasma glucose concentrations. Energy expenditure increased in the GH-group. GH-IGF-1 prevented a decrease in muscle polyribosomes indicating a preserved muscle protein synthesis. In the GH group unaltered BCAA and AAA levels were seen in muscle indicating an unchanged protein breakdown, while the other groups showed increased muscle concentrations postoperatively. Without statistically difference GH marginally improved the nitrogen balance, in terms of higher values, and growth factors improved the nitrogen balance when the shift in urea was taken into account. To conclude, growth factors influences urea metabolism, protein degradation and protein synthesis. There was no clearcut additional effect when combining GH and IGF-1 but the study was probably underpowered to outrule this and effects on nitrogen balance.

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Effect of rhGH and rhIGF-I treatment on protein utilization in elderly women

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1997.272.1.e94 ◽

1997 ◽

Vol 272 (1) ◽

pp. E94-E99 ◽

Cited By ~ 13

Author(s):

G. E. Butterfield ◽

J. Thompson ◽

M. J. Rennie ◽

R. Marcus ◽

R. L. Hintz ◽

...

Keyword(s):

Protein Synthesis ◽

Growth Factor ◽

Nitrogen Balance ◽

Elderly Women ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Whole Body ◽

High Dose ◽

Protein Utilization ◽

Body Protein

To assess the effect of recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor I (rhIGF-I) on protein utilization, 14 women, age 66-82 yr, were invited to participate in studies of nitrogen balance (n = 14), whole body protein turnover (n = 14), and muscle protein synthesis (n = 8). They were studied both 1 wk before and during the last week of a 1-mo regimen, to which they had been randomly assigned, of either 0.025 mg rhGH/kg once daily or rhIGF-I at 0.015 (low), 0.03 (mid), or 0.06 (high) mg/kg twice daily. Nitrogen balance increased significantly after 1 wk of treatment in all groups (P < 0.05). After 1 mo, the magnitude of this effect had diminished by 50% in the rhGH group but remained elevated throughout the treatment period with all doses of rhIGF-I. Both protein synthesis and breakdown, measured by a primed constant infusion of [15N]glycine, were significantly increased with rhGH (9% and 8%, respectively), low-dose rhIGF-I (4.5% and 4%), and high-dose rhIGF-I (18% and 17%). Net synthesis was significantly increased with rhGH (48%) and high- and mid-dose rhIGF-I (27% and 196%, respectively). Muscle protein synthesis as measured by incorporation of [1-13C]leucine increased significantly with rhGH (50%) and the mid (67%) and high (57%) doses of rhIGF-I. These data show that whole body and muscle protein synthesis are responsive to growth factor stimulation in elderly women.

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The response of muscle protein synthesis following whole-body resistance exercise is greater following 40 g than 20 g of ingested whey protein

Physiological Reports ◽

10.14814/phy2.12893 ◽

2016 ◽

Vol 4 (15) ◽

pp. e12893 ◽

Cited By ~ 75

Author(s):

Lindsay S. Macnaughton ◽

Sophie L. Wardle ◽

Oliver C. Witard ◽

Chris McGlory ◽

D. Lee Hamilton ◽

...

Keyword(s):

Protein Synthesis ◽

Resistance Exercise ◽

Whey Protein ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Whole Body ◽

Body Resistance

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Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis

Journal of Applied Physiology ◽

10.1152/jappl.2001.91.3.1041 ◽

2001 ◽

Vol 91 (3) ◽

pp. 1041-1047 ◽

Cited By ~ 134

Author(s):

G. Parise ◽

S. Mihic ◽

D. MacLennan ◽

K. E. Yarasheski ◽

M. A. Tarnopolsky

Keyword(s):

Protein Synthesis ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Fat Free Mass ◽

Whole Body ◽

Synthetic Rate ◽

Fractional Synthetic Rate ◽

Before And After ◽

Total Creatine ◽

Plasma Leucine

Creatine monohydrate (CrM) supplementation during resistance exercise training results in a greater increase in strength and fat-free mass than placebo. Whether this is solely due to an increase in intracellular water or whether there may be alterations in protein turnover is not clear at this point. We examined the effects of CrM supplementation on indexes of protein metabolism in young healthy men ( n = 13) and women ( n = 14). Subjects were randomly allocated to CrM (20 g/day for 5 days followed by 5 g/day for 3–4 days) or placebo (glucose polymers) and tested before and after the supplementation period under rigorous dietary and exercise controls. Muscle phosphocreatine, creatine, and total creatine were measured before and after supplementation. A primed-continuous intravenous infusion of l-[1-13C]leucine and mass spectrometry were used to measure mixed-muscle protein fractional synthetic rate and indexes of whole body leucine metabolism (nonoxidative leucine disposal), leucine oxidation, and plasma leucine rate of appearance. CrM supplementation increased muscle total creatine (+13.1%, P < 0.05) with a trend toward an increase in phosphocreatine (+8.8%, P = 0.09). CrM supplementation did not increase muscle fractional synthetic rate but reduced leucine oxidation (−19.6%) and plasma leucine rate of appearance (−7.5%, P < 0.05) in men, but not in women. CrM did not increase total body mass or fat-free mass. We conclude that short-term CrM supplementation may have anticatabolic actions in some proteins (in men), but CrM does not increase whole body or mixed-muscle protein synthesis.

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Dose-response effects of dietary protein on muscle protein synthesis during recovery from endurance exercise in young men: a double-blind randomized trial

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa073 ◽

2020 ◽

Vol 112 (2) ◽

pp. 303-317 ◽

Cited By ~ 5

Author(s):

Tyler A Churchward-Venne ◽

Philippe J M Pinckaers ◽

Joey S J Smeets ◽

Milan W Betz ◽

Joan M Senden ◽

...

Keyword(s):

Protein Synthesis ◽

G Protein ◽

Endurance Exercise ◽

Dietary Protein ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Mitochondrial Protein ◽

Whole Body ◽

Double Blind ◽

Body Protein

ABSTRACT Background Protein ingestion increases skeletal muscle protein synthesis rates during recovery from endurance exercise. Objectives We aimed to determine the effect of graded doses of dietary protein co-ingested with carbohydrate on whole-body protein metabolism, and skeletal muscle myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis rates during recovery from endurance exercise. Methods In a randomized, double-blind, parallel-group design, 48 healthy, young, endurance-trained men (mean ± SEM age: 27 ± 1 y) received a primed continuous infusion of l-[ring-2H5]-phenylalanine, l-[ring-3,5-2H2]-tyrosine, and l-[1-13C]-leucine and ingested 45 g carbohydrate with either 0 (0 g PRO), 15 (15 g PRO), 30 (30 g PRO), or 45 (45 g PRO) g intrinsically l-[1-13C]-phenylalanine and l-[1-13C]-leucine labeled milk protein after endurance exercise. Blood and muscle biopsy samples were collected over 360 min of postexercise recovery to assess whole-body protein metabolism and both MyoPS and MitoPS rates. Results Protein intake resulted in ∼70%–74% of the ingested protein-derived phenylalanine appearing in the circulation. Whole-body net protein balance increased dose-dependently after ingestion of 0, 15, 30, or 45 g protein (mean ± SEM: −0.31± 0.16, 5.08 ± 0.21, 10.04 ± 0.30, and 13.49 ± 0.55 μmol phenylalanine · kg−1 · h−1, respectively; P < 0.001). 30 g PRO stimulated a ∼46% increase in MyoPS rates (%/h) compared with 0 g PRO and was sufficient to maximize MyoPS rates after endurance exercise. MitoPS rates were not increased after protein ingestion; however, incorporation of dietary protein–derived l-[1-13C]-phenylalanine into de novo mitochondrial protein increased dose-dependently after ingestion of 15, 30, and 45 g protein at 360 min postexercise (0.018 ± 0.002, 0.034 ± 0.002, and 0.046 ± 0.003 mole percentage excess, respectively; P < 0.001). Conclusions Protein ingested after endurance exercise is efficiently digested and absorbed into the circulation. Whole-body net protein balance and dietary protein–derived amino acid incorporation into mitochondrial protein respond to increasing protein intake in a dose-dependent manner. Ingestion of 30 g protein is sufficient to maximize MyoPS rates during recovery from a single bout of endurance exercise. This trial was registered at trialregister.nl as NTR5111.

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Coordinated increase in albumin, fibrinogen, and muscle protein synthesis during hemodialysis: role of cytokines

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00444.2003 ◽

2004 ◽

Vol 286 (4) ◽

pp. E658-E664 ◽

Cited By ~ 38

Author(s):

Dominic S. C. Raj ◽

Elizabeth A. Dominic ◽

Robert Wolfe ◽

Vallabh O. Shah ◽

Arthur Bankhurst ◽

...

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Whole Body ◽

Constant Infusion ◽

Fractional Synthesis ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

Serum albumin, fibrinogen levels, and lean body mass are important predictors of outcome in end-stage renal disease (ESRD). We estimated the fractional synthesis rates of albumin (FSR-A), fibrinogen (FSR-F), and muscle protein (FSR-M) in nine ESRD patients and eight controls, using primed constant infusion of l-[ ring-13C6]phenylalanine. Cytokine profile and arteriovenous balance of amino acids were also measured. ESRD patients were studied before (Pre-HD) and during hemodialysis (HD). Plasma IL-6, IL-10, and C-reactive protein increased significantly during HD. Despite a decrease in the delivery of amino acids to the leg, the outflow of the amino acids increased during HD. The net balance of amino acids became more negative during HD, indicating release from the muscle. HD increased leg muscle protein synthesis (45%) and catabolism (108%) but decreased whole body proteolysis (15%). FSR-A during HD (9.7 ± 0.9%/day) was higher than pre-HD (6.5 ± 0.9%/day) and controls (5.8 ± 0.5%/day, P < 0.01). FSR-F increased during HD (19.7 ± 2.6%/day vs. 11.8 ± 0.6%/day, P < 0.01), but it was not significantly different from that of controls (14.4 ± 1.4%/day). FSR-M intradialysis (1.77 ± 0.19%/day) was higher than pre-HD (1.21 ± 0.25%/day) and controls (1.30 ± 0.32%/day, P < 0.001). Pre-HD FSR-A, FSR-F, and FSR-M values were comparable to those of controls. There was a significant and positive correlation between plasma IL-6 and the FSRs. Thus, in ESRD patients without metabolic acidosis, the fractional synthesis rates of albumin, fibrinogen, and muscle protein are not decreased pre-HD. However, HD increases the synthesis of albumin, fibrinogen, and muscle protein. The coordinated increase in the FSRs is facilitated by constant delivery of amino acids derived from the muscle catabolism and intradialytic increase in IL-6.

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Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00413.2004 ◽

2005 ◽

Vol 288 (4) ◽

pp. E645-E653 ◽

Cited By ~ 166

Author(s):

René Koopman ◽

Anton J. M. Wagenmakers ◽

Ralph J. F. Manders ◽

Antoine H. G. Zorenc ◽

Joan M. G. Senden ◽

...

Keyword(s):

Protein Synthesis ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Whole Body ◽

Vastus Lateralis Muscle ◽

Protein Balance ◽

Body Protein ◽

Breakdown Rates ◽

Postexercise Recovery ◽

Male Subjects

The present study was designed to determine postexercise muscle protein synthesis and whole body protein balance following the combined ingestion of carbohydrate with or without protein and/or free leucine. Eight male subjects were randomly assigned to three trials in which they consumed drinks containing either carbohydrate (CHO), carbohydrate and protein (CHO+PRO), or carbohydrate, protein, and free leucine (CHO+PRO+Leu) following 45 min of resistance exercise. A primed, continuous infusion of l-[ ring-13C6]phenylalanine was applied, with blood samples and muscle biopsies collected to assess fractional synthetic rate (FSR) in the vastus lateralis muscle as well as whole body protein turnover during 6 h of postexercise recovery. Plasma insulin response was higher in the CHO+PRO+Leu compared with the CHO and CHO+PRO trials (+240 ± 19% and +77 ± 11%, respectively, P < 0.05). Whole body protein breakdown rates were lower, and whole body protein synthesis rates were higher, in the CHO+PRO and CHO+PRO+Leu trials compared with the CHO trial ( P < 0.05). Addition of leucine in the CHO+PRO+Leu trial resulted in a lower protein oxidation rate compared with the CHO+PRO trial. Protein balance was negative during recovery in the CHO trial but positive in the CHO+PRO and CHO+PRO+Leu trials. In the CHO+PRO+Leu trial, whole body net protein balance was significantly greater compared with values observed in the CHO+PRO and CHO trials ( P < 0.05). Mixed muscle FSR, measured over a 6-h period of postexercise recovery, was significantly greater in the CHO+PRO+Leu trial compared with the CHO trial (0.095 ± 0.006 vs. 0.061 ± 0.008%/h, respectively, P < 0.05), with intermediate values observed in the CHO+PRO trial (0.0820 ± 0.0104%/h). We conclude that coingestion of protein and leucine stimulates muscle protein synthesis and optimizes whole body protein balance compared with the intake of carbohydrate only.

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Muscle Protein Synthesis and Whole-Body Protein Turnover Responses to Ingesting Essential Amino Acids, Intact Protein, and Protein-Containing Mixed Meals with Considerations for Energy Deficit

Nutrients ◽

10.3390/nu12082457 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2457 ◽

Cited By ~ 3

Author(s):

Jess A. Gwin ◽

David D. Church ◽

Robert R. Wolfe ◽

Arny A. Ferrando ◽

Stefan M. Pasiakos

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Protein Turnover ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Energy Deficit ◽

Whole Body ◽

Intact Protein ◽

Body Protein ◽

Protein Feeding

Protein intake recommendations to optimally stimulate muscle protein synthesis (MPS) are derived from dose-response studies examining the stimulatory effects of isolated intact proteins (e.g., whey, egg) on MPS in healthy individuals during energy balance. Those recommendations may not be adequate during periods of physiological stress, specifically the catabolic stress induced by energy deficit. Providing supplemental intact protein (20–25 g whey protein, 0.25–0.3 g protein/kg per meal) during strenuous military operations that elicit severe energy deficit does not stimulate MPS-associated anabolic signaling or attenuate lean mass loss. This occurs likely because a greater proportion of the dietary amino acids consumed are targeted for energy-yielding pathways, whole-body protein synthesis, and other whole-body essential amino acid (EAA)-requiring processes than the proportion targeted for MPS. Protein feeding formats that provide sufficient energy to offset whole-body energy and protein-requiring demands during energy deficit and leverage EAA content, digestion, and absorption kinetics may optimize MPS under these conditions. Understanding the effects of protein feeding format-driven alterations in EAA availability and subsequent changes in MPS and whole-body protein turnover is required to design feeding strategies that mitigate the catabolic effects of energy deficit. In this manuscript, we review the effects, advantages, disadvantages, and knowledge gaps pertaining to supplemental free-form EAA, intact protein, and protein-containing mixed meal ingestion on MPS. We discuss the fundamental role of whole-body protein balance and highlight the importance of comprehensively assessing whole-body and muscle protein kinetics when evaluating the anabolic potential of varying protein feeding formats during energy deficit.

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Effects of growth hormone and an antiserum to rat growth hormone on serum IGF-I and muscle protein synthesis and accretion in the rat

Journal of Endocrinology ◽

10.1677/joe.0.1390395 ◽

1993 ◽

Vol 139 (3) ◽

pp. 395-401 ◽

Cited By ~ 4

Author(s):

R. M. Palmer ◽

D. J. Flint ◽

J. C. MacRae ◽

F. E. Fairhurst ◽

L. A. Bruce ◽

...

Keyword(s):

Growth Hormone ◽

Protein Synthesis ◽

Protein Content ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Polyclonal Antiserum ◽

Whole Body ◽

Total Protein Content ◽

Plantaris Muscle ◽

Igf I

ABSTRACT Rats were injected twice daily for up to 10 days with GH or with a polyclonal antiserum to rat GH, commencing at 21–22 days of age. Administration of bovine or human GH (1 mg/day) improved whole body growth rates by 22% and 29% respectively. Plantaris muscle mass was also increased, by 7 and 14% respectively. Anti-GH injected twice daily resulted in a 7% decrease in body weight at 4 days and a 10% reduction by 10 days. Similar decreases were observed in the total protein content of plantaris and soleus muscles. The decrease in the fractional rate of protein synthesis was proportionately greater than the decline in protein content in plantaris muscle whereas in the soleus no change in the rate of protein synthesis was observed, suggesting that the effect on this muscle was due to an increase in the rate of protein degradation. Serum total IGF-I was unchanged by treatment with either GH or anti-GH while the amount of hepatic IGF-I mRNA was also unaffected by anti-GH injection. These data are consistent with a direct effect of GH or an effect mediated by an autocrine/paracrine mechanism of action on muscle but do not support a role for serum total IGF-I as an endocrine mediator of GH action. Journal of Endocrinology (1993) 139, 395–401

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Impact of surgical trauma on human skeletal muscle protein synthesis

Clinical Science ◽

10.1042/cs20040192 ◽

2004 ◽

Vol 107 (6) ◽

pp. 601-607 ◽

Cited By ~ 6

Author(s):

Inga TJÄDER ◽

Pia ESSEN ◽

Peter J. GARLICK ◽

Margaret A. McMNURLAN ◽

Olav ROOYACKERS ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Pilot Study ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Major Surgery ◽

Synthesis Rate ◽

Protein Synthesis Rate ◽

Surgical Trauma ◽

Minor Surgery

Muscle protein catabolism is a considerable clinical problem following surgery. However, the impact of surgical trauma on muscle protein synthesis is not well characterized. In this pilot study, we therefore investigated whether the severity of surgical trauma is related to a decrease in muscle protein synthesis rate in humans. Metabolically healthy patients (n=28) were included in the study. Eight of the patients were day-care patients undergoing minor breast surgery (defined as minor surgery). The other 20 patients were subjected to major abdominal surgery and were therefore scheduled to stay overnight in the recovery room during the first postoperative night (defined as major surgery). Protein FSRs (fractional synthesis rates) in skeletal muscle were determined during a measurement period of 90 min before surgery and immediately after termination of surgery. FSR in skeletal muscle of the minor surgery patients was 1.72±0.25%/24 h before surgery and 1.67±0.29%/24 h after surgery (P=0.68). In the major surgery group, FSR was 1.62±0.30%/24 h before surgery and 1.57±0.40%/24 h (P=0.59) immediately following surgery. The observations made in this pilot study could not confirm a size-related decrease in muscle protein synthesis immediately following minor and major surgery. This finding is discussed in relation to confounders, postoperative course and to muscle protein degradation. The shortage of knowledge in this field is emphasized.

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