Differential effect of sepsis on ability of leucine and IGF-I to stimulate muscle translation initiation

2004 ◽  
Vol 287 (4) ◽  
pp. E721-E730 ◽  
Author(s):  
Charles H. Lang ◽  
Robert A. Frost
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Growth Factor ◽  
Translation Initiation ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Growth Factor I ◽  
Signaling Components

Polymicrobial sepsis impairs skeletal muscle protein synthesis, which results from impairment in translation initiation under basal conditions. The purpose of the present study was to test the hypothesis that sepsis also impairs the anabolic response to amino acids, specifically leucine (Leu). Sepsis was induced by cecal ligation and puncture, and 24 h later, Leu or saline (Sal) was orally administered to septic and time-matched nonseptic rats. The gastrocnemius was removed 20 min later for assessment of protein synthesis and signaling components important in peptide-chain initiation. Oral Leu increased muscle protein synthesis in nonseptic rats. Leu was unable to increase protein synthesis in muscle from septic rats, and synthetic rates remained below those observed in nonseptic + Sal rats. In nonseptic + Leu rats, phosphorylation of eukaryotic initiation factor (eIF)4E-binding protein 1 (4E-BP1) in muscle was markedly increased compared with values from time-matched Sal-treated nonseptic rats. This change was associated with redistribution of eIF4E from the inactive eIF4E·4E-BP1 to the active eIF4E·eIF4G complex. In septic rats, Leu-induced phosphorylation of 4E-BP1 and changes in eIF4E distribution were completely abrogated. Sepsis also antagonized the Leu-induced increase in phosphorylation of S6 kinase 1 and ribosomal protein S6. Sepsis attenuated Leu-induced phosphorylation of mammalian target of rapamycin and eIF4G. The ability of sepsis to inhibit anabolic effects of Leu could not be attributed to differences in plasma concentrations of insulin, insulin-like growth factor I, or Leu between groups. In contrast, the ability of exogenous insulin-like growth factor I to stimulate the same signaling components pertaining to translation initiation was not impaired by sepsis. Hence, sepsis produces a relatively specific Leu resistance in skeletal muscle that impairs the ability of this amino acid to stimulate translation initiation and protein synthesis.

scholarly journals Severe diabetes prohibits elevations in muscle protein synthesis after acute resistance exercise in rats

2000 ◽  
Vol 88 (1) ◽  
pp. 102-108 ◽  
Author(s):  
Mark J. Fedele ◽  
Jazmir M. Hernandez ◽  
Charles H. Lang ◽  
Thomas C. Vary ◽  
Scot R. Kimball ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Growth Factor ◽  
Resistance Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Critical Concentration ◽  
Diabetic Rats ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Growth Factor I

This study determined whether rates of protein synthesis increase after acute resistance exercise in skeletal muscle from severely diabetic rats. Previous studies consistently show that postexercise rates of protein synthesis are elevated in nondiabetic and moderately diabetic rats. Severely diabetic rats performed acute resistance exercise ( n= 8) or remained sedentary ( n = 8). A group of nondiabetic age-matched rats served as controls ( n = 9). Rates of protein synthesis were measured 16 h after exercise. Plasma glucose concentrations were >500 mg/dl in the diabetic rats. Rates of protein synthesis (nmol phenylalanine incorporated ⋅ g muscle−1 ⋅ h−1, means ± SE) were not different between exercised (117 ± 7) and sedentary (106 ± 9) diabetic rats but were significantly ( P < 0.05) lower than in sedentary nondiabetic rats (162 ± 9) and in exercised nondiabetic rats (197 ± 7). Circulating insulin concentrations were 442 ± 65 pM in nondiabetic rats and 53 ± 11 and 72 ± 19 pM in sedentary and exercised diabetic rats, respectively. Plasma insulin-like growth factor I concentrations were reduced by 33% in diabetic rats compared with nondiabetic rats, and there was no difference between exercised and sedentary diabetic rats. Muscle insulin-like growth factor I was not affected by resistance exercise in diabetic rats. The results show that there is a critical concentration of insulin below which rates of protein synthesis begin to decline in vivo. In contrast to previous studies using less diabetic rats, severely diabetic rats cannot increase rates of protein synthesis after acute resistance exercise.

Developmental regulation of the activation of signaling components leading to translation initiation in skeletal muscle of neonatal pigs

2006 ◽  
Vol 291 (4) ◽  
pp. E849-E859 ◽  
Author(s):  
Agus Suryawan ◽  
Jeffery Escobar ◽  
Jason W. Frank ◽  
Hanh V. Nguyen ◽  
Teresa A. Davis
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Growth Factor ◽  
Translation Initiation ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Developmental Regulation ◽  
Skeletal Muscle Protein ◽  
Skeletal Muscle Protein Synthesis ◽  
Signaling Components

The rapid growth of neonates is driven by high rates of skeletal muscle protein synthesis. This high rate of protein synthesis, which is induced by feeding, declines with development. Overnight-fasted 7- and 26-day-old pigs either remained fasted or were refed, and the abundance and phosphorylation of growth factor- and nutrient-induced signaling components that regulate mRNA translation initiation were measured in skeletal muscle and liver. In muscle, but not liver, the activation of inhibitors of protein synthesis, phosphatase and tensin homolog deleted on chromosome 10, protein phosphatase 2A, and tuberous sclerosis complex 1/2 increased with age. Serine/threonine phosphorylation of the insulin receptor and insulin receptor substrate-1, which downregulates insulin signaling, and the activation of AMP-activated protein kinase, an inhibitor of protein synthesis, were unaffected by age and feeding in muscle and liver. Activation of positive regulators of protein synthesis, mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase 1 (S6K1), and eIF4E-binding protein-1 (4E-BP1) decreased with age in muscle but not liver. Feeding enhanced mTOR, S6K1, and 4E-BP1 activation in muscle, and this response decreased with age. In liver, activation of S6K1 and 4E-BP1, but not mTOR, was increased by feeding but was unaffected by age. Raptor abundance and the association between raptor and mTOR were greater in 7- than in 26-day-old pigs. The results suggest that the developmental decline in skeletal muscle protein synthesis is due in part to developmental regulation of the activation of growth factor and nutrient-signaling components.

Relationship of Insulin-Like Growth Factor-I to Muscle Protein Synthesis in Fasted Chicks.

1998 ◽  
Vol 35 (5) ◽  
pp. 263-270 ◽  
Author(s):  
Kazumi KITA ◽  
Takako SHIBATA ◽  
M.AMAN YAMAN ◽  
Michael A. CONLON ◽  
Takeshi SASAKI ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Growth Factor ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Growth Factor I ◽  
Relationship Of

scholarly journals Short-Term Oxandrolone Administration Stimulates Net Muscle Protein Synthesis in Young Men1

1999 ◽  
Vol 84 (8) ◽  
pp. 2705-2711 ◽  
Author(s):  
Melinda Sheffield-Moore ◽  
Randall J. Urban ◽  
Steven E. Wolf ◽  
J. Jiang ◽  
Don H. Catlin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Growth Factor ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Rt Pcr ◽  
Short Term ◽  
Healthy Men ◽  
Factor I

Short term administration of testosterone stimulates net protein synthesis in healthy men. We investigated whether oxandrolone[ Oxandrin (OX)], a synthetic analog of testosterone, would improve net muscle protein synthesis and transport of amino acids across the leg. Six healthy men [22 ± 1 (±se) yr] were studied in the postabsorptive state before and after 5 days of oral OX (15 mg/day). Muscle protein synthesis and breakdown were determined by a three-compartment model using stable isotopic data obtained from femoral arterio-venous sampling and muscle biopsy. The precursor-product method was used to determine muscle protein fractional synthetic rates. Fractional breakdown rates were also directly calculated. Total messenger ribonucleic acid (mRNA) concentrations of skeletal muscle insulin-like growth factor I and androgen receptor (AR) were determined using RT-PCR. Model-derived muscle protein synthesis increased from 53.5 ± 3 to 68.3 ± 5 (mean ± se) nmol/min·100 mL/leg (P &lt; 0.05), whereas protein breakdown was unchanged. Inward transport of amino acids remained unchanged with OX, whereas outward transport decreased (P &lt; 0.05). The fractional synthetic rate increased 44% (P &lt; 0.05) after OX administration, with no change in fractional breakdown rate. Therefore, the net balance between synthesis and breakdown became more positive with both methodologies (P &lt; 0.05) and was not different from zero. Further, RT-PCR showed that OX administration significantly increased mRNA concentrations of skeletal muscle AR without changing insulin-like growth factor I mRNA concentrations. We conclude that short term OX administration stimulated an increase in skeletal muscle protein synthesis and improved intracellular reutilization of amino acids. The mechanism for this stimulation may be related to an OX-induced increase in AR expression in skeletal muscle.

scholarly journals INSULIN-LIKE GROWTH FACTOR-I STIMULATES PROTEIN SYNTHESIS IN SKELETAL MUSCLE IN THE NEONATE, BUT NOT LIVER AND GUT

2001 ◽  
Vol 33 (5) ◽  
pp. S328
Author(s):  
J A. Bush ◽  
H V. Nguyen ◽  
A Suryawan ◽  
P R. Beckett ◽  
M L. Fiorotto ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Growth Factor I

scholarly journals Skeletal and cardiac myopathy in HIV-1 transgenic rats

2008 ◽  
Vol 295 (4) ◽  
pp. E964-E973 ◽  
Author(s):  
Anne M. Pruznak ◽  
Ly Hong-Brown ◽  
Rachel Lantry ◽  
Pengxiang She ◽  
Robert A. Frost ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Growth Factor ◽  
Muscle Atrophy ◽  
Cardiac Mass ◽  
Whole Body ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Growth Factor I ◽  
Hiv 1

The mechanism by which human immunodeficiency virus (HIV)-1 infection in humans leads to the erosion of lean body mass is poorly defined. Therefore, the purpose of the present study was to determine whether transgenic (Tg) rats that constitutively overexpress HIV-1 viral proteins exhibit muscle wasting and to elucidate putative mechanisms. Over 7 mo, Tg rats gained less body weight than pair-fed controls exclusively as a result of a proportional reduction in lean, not fat, mass. Fast- and slow-twitch muscle atrophy in Tg rats did not result from a reduction in the in vivo-determined rate of protein synthesis. In contrast, urinary excretion of 3-methylhistidine, as well as the content of atrogin-1 and the 14-kDa actin fragment, was elevated in gastrocnemius of Tg rats, suggesting increased muscle proteolysis. Similarly, Tg rats had reduced cardiac mass, which was independent of a change in protein synthesis. This decreased cardiac mass was associated with a reduction in stroke volume, but cardiac output was maintained by a compensatory increase in heart rate. The HIV-induced muscle atrophy was associated with increased whole body energy expenditure, which was not due to an elevated body temperature or secondary bacterial infection. Furthermore, the atrophic response could not be attributed to the development of insulin resistance, decreased levels of circulating amino acids, or increased tissue cytokines. However, skeletal muscle and, to a lesser extent, circulating insulin-like growth factor I was reduced in Tg rats. Although hepatic injury was implicated by increased plasma levels of aspartate and alanine aminotransferases, hepatic protein synthesis was not different between control and Tg rats. Hence, HIV-1 Tg rats develop atrophy of cardiac and skeletal muscle, the latter of which results primarily from an increased protein degradation and may be related to the marked reduction in muscle insulin-like growth factor I.

Sign in / Sign up

Export Citation Format

Share Document