Role of eIF4E in stimulation of protein synthesis by IGF-I in perfused rat skeletal muscle

2000 ◽  
Vol 278 (1) ◽  
pp. E58-E64 ◽  
Author(s):  
Thomas C. Vary ◽  
Leonard S. Jefferson ◽  
Scot R. Kimball
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Initiation Factor ◽  
Translational Efficiency ◽  
Rat Skeletal Muscle ◽  
Phosphorylation State ◽  
Factor I ◽  
Igf I ◽  
Stimulation Of

Insulin-like growth factor I (IGF-I) promotes anabolism by stimulating protein synthesis in skeletal muscle. In the present study, we have examined mechanisms by which IGF-I stimulates protein synthesis in skeletal muscle with a perfused rat hindlimb preparation. IGF-I (10 nM) stimulated protein synthesis over 2.7-fold. Total RNA content was unaffected, but translational efficiency was increased by IGF-I. We next examined the effect of IGF-I on eukaryotic initiation factor (eIF) 4E as a mechanism regulating translation initiation. IGF-I did not alter either the amount of eIF4E associated with the eIF4E binding protein 4E-BP1 or the phosphorylation state of 4E-BP1. Likewise, the phosphorylation state of eIF4E was unaltered by IGF-I. In contrast, the amount of eIF4E bound to eIF4G was increased threefold by IGF-I. We conclude that IGF-I regulates protein synthesis in skeletal muscle by enhancing formation of the active eIF4E ⋅ eIF4G complex.

Insulin-like growth factor I accelerates protein synthesis in skeletal muscle during sepsis

1995 ◽  
Vol 269 (5) ◽  
pp. E977-E981 ◽  
Author(s):  
C. V. Jurasinski ◽  
T. C. Vary
Keyword(s):  
Protein Synthesis ◽  
Growth Factor ◽  
Peptide Chain ◽  
Translational Efficiency ◽  
Insulin Like Growth Factor ◽  
Recombinant Human Insulin ◽  
Chain Initiation ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Sepsis causes an inhibition of protein synthesis in gastrocnemius that is resistant to the anabolic effects of insulin. The purpose of the present studies was to investigate the effect of recombinant human insulin-like growth factor I (IGF-I) on protein synthesis during a 30-min perfusion of the isolated rat hindlimb from septic rats. Inclusion of IGF-I (1 or 10 nM) in the perfusate stimulated protein synthesis in gastrocnemius of septic rats 2.5-fold and restored rates of protein synthesis to those observed in control rats. The stimulation of protein synthesis did not result from an increase in the RNA content but was correlated with a 2.5-fold increase in the translational efficiency. The enhanced translational efficiency was accompanied by a 33 and 55% decrease in the abundance of free 40S and 60S ribosomal subunits, respectively, indicating that IGF-I accelerated peptide-chain initiation relative to elongation/termination. These studies provide evidence that IGF-I can accelerate protein synthesis in gastrocnemius during chronic sepsis by reversing the sepsis-induced inhibition of peptide-chain initiation.

Role of insulin and IGF-I in activation of muscle protein synthesis after oral feeding

1996 ◽  
Vol 270 (4) ◽  
pp. E614-E620 ◽  
Author(s):  
E. Svanberg ◽  
H. Zachrisson ◽  
C. Ohlsson ◽  
B. M. Iresjo ◽  
K. G. Lundholm
Keyword(s):  
Protein Synthesis ◽  
Skeletal Muscles ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Oral Feeding ◽  
Myofibrillar Proteins ◽  
Diabetic Mice ◽  
Igf I ◽  
Stimulation Of

The aim was to evaluate the role of insulin and insulin-like growth factor I (IGF-I) in activation of muscle protein synthesis after oral feeding. Synthesis rate of globular and myofibrillar proteins in muscle tissue was quantified by a flooding dose of radioactive phenylalanine. Muscle tissue expression of IGF-I mRNA was measured. Normal (C57 Bl) and diabetic mice (type I and type II) were subjected to an overnight fast (18 h) with subsequent refeeding procedures for 3 h with either oral chow intake or provision of insulin, IGF-I, glucose, and amino acids. Anti-insulin and anti-IGF-I were provided intraperitoneally before oral refeeding in some experiments. An overnight fast reduced synthesis of both globular (38 +/- 3%) and myofibrillar proteins (54 +/- 3%) in skeletal muscles, which was reversed by oral refeeding. Muscle protein synthesis, after starvation/ refeeding, was proportional and similar to changes in skeletal muscle IGF-I mRNA expression. Diabetic mice responded quantitatively similarly to starvation/refeeding in muscle protein synthesis compared with normal mice (C57 Bl). Both anti-insulin and anti-IGF-I attenuated significantly the stimulation of muscle protein synthesis in response to oral feeding, whereas exogenous provision of either insulin or IGF-I to overnight-starved and freely fed mice did not clearly stimulate protein synthesis in skeletal muscles. Our results support the suggestion that insulin and IGF-I either induce or facilitate the protein synthesis machinery in skeletal muscles rather than exerting a true stimulation of the biosynthetic process during feeding.

scholarly journals Insulin-Like Growth Factor I Circumvents Defective Insulin Action in Human Myotonic Dystrophy Skeletal Muscle Cells1

Endocrinology ◽  
1999 ◽  
Vol 140 (9) ◽  
pp. 4244-4250 ◽  
Author(s):  
Denis Furling ◽  
André Marette ◽  
Jack Puymirat
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Growth Factor ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Insulin Action ◽  
Factor I ◽  
Impaired Insulin ◽  
Igf I ◽  
Impaired Insulin Action

Abstract Primary human skeletal muscle cell cultures derived from muscles of a myotonic dystrophy (DM) fetus provided a model in which both resistance to insulin action described in DM patient muscles and the potential ability of insulin-like growth factor I (IGF-I) to circumvent this defect could be investigated. Basal glucose uptake was the same in cultured DM cells as in normal myotubes. In DM cells, a dose of 10 nm insulin produced no stimulatory effect on glucose uptake, and at higher concentrations, stimulation of glucose uptake remained significantly lower than that in normal myotubes. In addition, basal and insulin-mediated protein synthesis were both significantly reduced compared with those in normal cells. In DM myotubes, insulin receptor messenger RNA expression and insulin receptor binding were significantly diminished, whereas the expression of GLUT1 and GLUT4 glucose transporters was not affected. These results indicate that impaired insulin action is retained in DM cultured myotubes. The action of recombinant human IGF-I (rhIGF-I) was evaluated in this cellular model. We showed that rhIGF-I is able to stimulate glucose uptake to a similar extent as in control cells and restore normal protein synthesis level in DM myotubes. Thus, rhIGF-I is able to bypass impaired insulin action in DM myotubes. This provides a solid foundation for the eventual use of rhIGF-I as an effective treatment of muscle weakness and wasting in DM.

scholarly journals Skeletal muscle and resistance exercise training; the role of protein synthesis in recovery and remodeling

2017 ◽  
Vol 122 (3) ◽  
pp. 541-548 ◽  
Author(s):  
Chris McGlory ◽  
Michaela C. Devries ◽  
Stuart M. Phillips
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Turnover ◽  
Potential Role ◽  
Muscle Protein ◽  
Short Review ◽  
Translational Efficiency ◽  
Exercise Science ◽  
Resistance Exercise Training

Exercise results in the rapid remodeling of skeletal muscle. This process is underpinned by acute and chronic changes in both gene and protein synthesis. In this short review we provide a brief summary of our current understanding regarding how exercise influences these processes as well as the subsequent impact on muscle protein turnover and resultant shift in muscle phenotype. We explore concepts of ribosomal biogenesis and the potential role of increased translational capacity vs. translational efficiency in contributing to muscular hypertrophy. We also examine whether high-intensity sprinting-type exercise promotes changes in protein turnover that lead to hypertrophy or merely a change in mitochondrial content. Finally, we propose novel areas for future study that will fill existing knowledge gaps in the fields of translational research and exercise science.

IGF-I/IGFBP-3 binary complex modulates sepsis-induced inhibition of protein synthesis in skeletal muscle

2000 ◽  
Vol 279 (5) ◽  
pp. E1145-E1158 ◽  
Author(s):  
Elisabeth Svanberg ◽  
Robert A. Frost ◽  
Charles H. Lang ◽  
Jorgen Isgaard ◽  
Leonard S. Jefferson ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Binding Protein ◽  
Initiation Factor ◽  
Translational Efficiency ◽  
Binary Complex ◽  
Igf I ◽  
Inhibition Of Protein Synthesis ◽  
Values Assessment ◽  
Igf Binding ◽  
Igfbp 3

The present study evaluated the ability of insulin-like growth factor I (IGF-I) complexed with IGF binding protein-3 (IGFBP-3) to modulate the sepsis-induced inhibition of protein synthesis in gastrocnemius. Beginning 16 h after the induction of sepsis, either the binary complex or saline was injected twice daily via a tail vein, with measurements made 3 and 5 days later. By day 3, sepsis had reduced plasma IGF-I concentrations ∼50% in saline-treated rats. Administration of the binary complex provided exogenous IGF-I to compensate for the sepsis-induced diminished plasma IGF-I. Sepsis decreased rates of protein synthesis in gastrocnemius relative to controls by limiting translational efficiency. Treatment of septic rats with the binary complex for 5 days attenuated the sepsis-induced inhibition of protein synthesis and restored translational efficiency to control values. Assessment of potential mechanisms regulating translational efficiency showed that neither the sepsis-induced change in gastrocnemius content of eukaryotic initiation factor 2B (eIF2B), the amount of eIF4E associated with 4E binding protein-1 (4E-BP1), nor the phosphorylation state of 4E-BP1 or eIF4E were altered by the binary complex. Overall, the results are consistent with the hypothesis that decreases in plasma IGF-I are partially responsible for enhanced muscle catabolism during sepsis.

scholarly journals Ectopic expression of eIF2Bε in rat skeletal muscle rescues the sepsis-induced reduction in guanine nucleotide exchange activity and protein synthesis

2010 ◽  
Vol 299 (2) ◽  
pp. E241-E248 ◽  
Author(s):  
Alexander P. Tuckow ◽  
Thomas C. Vary ◽  
Scot R. Kimball ◽  
Leonard S. Jefferson
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Ectopic Expression ◽  
Initiation Factor ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Rat Skeletal Muscle ◽  
Guanine Nucleotide Exchange

Eukaryotic initiation factor 2B (eIF2B) is a guanine nucleotide exchange factor (GEF) whose activity is both tightly regulated and rate-controlling with regard to global rates of protein synthesis. Skeletal muscle eIF2B activity and expression of its catalytic ε-subunit (eIF2Bε) have been implicated as potential contributors to the altered rates of protein synthesis in a number of physiological conditions and experimental models. The objective of this study was to directly examine the effects of exogenously expressed eIF2Bε in vivo on GEF activity and protein synthetic rates in rat skeletal muscle. A plasmid encoding FLAG-eIF2Bε was transfected into the tibialis anterior (TA) of one leg, while the contralateral TA received a control plasmid. Ectopic expression of eIF2Bε resulted in increased GEF activity in TA homogenates of healthy rats, demonstrating that the expressed protein was catalytically active. In an effort to restore a deficit in eIF2B activity, we utilized an established model of chronic sepsis in which skeletal muscle eIF2B activity is known to be impaired. Ectopic expression of eIF2Bε in the TA rescued the sepsis-induced deficit in GEF activity and muscle protein synthesis. The results demonstrate that modulation of eIF2Bε expression may be sufficient to correct deficits in skeletal muscle protein synthesis associated with sepsis and other muscle-wasting conditions.

Phenylarsine oxide and denervation effects on hormone-stimulated glucose transport

1988 ◽  
Vol 255 (2) ◽  
pp. E159-E165 ◽  
Author(s):  
M. O. Sowell ◽  
K. A. Robinson ◽  
M. G. Buse
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Insulin Action ◽  
Denervated Muscle ◽  
Phenylarsine Oxide ◽  
Early Step ◽  
Factor I ◽  
Igf I ◽  
Receptor Number ◽  
Stimulation Of

Insulin and insulin-like growth factor I (IGF-I) stimulate glucose transport in skeletal muscle through separate receptors. The proximal postreceptor events in coupling insulin and IGF-I receptors to glucose transport have been suggested to differ. Denervation of skeletal muscle produces a postreceptor insulin resistance presumably at an early step in the signaling cascade. We examined the effects of denervation and phenylarsine oxide (PAO), an agent believed to block insulin action on transport at a postreceptor step, on insulin and IGF-I stimulated 2-deoxy-D-glucose transport in isolated solei. Denervation (24 h) produced severe IGF-I resistance without affecting IGF-I receptor number or affinity. PAO inhibited insulin and IGF-I stimulation of transport in control muscles by approximately 90 and approximately 70%, respectively. In denervated muscle PAO inhibited transport stimulation by both hormones less than in controls. Conclusions are that 1) skeletal muscle insulin and IGF-I receptors signal transport mainly through a PAO-sensitive mechanism, but IGF-I's action involves a larger PAO-resistant component; 2) the denervation-induced postreceptor resistance of glucose transport to both hormones involves primarily the PAO-sensitive pathway.

Growth hormone regulates the level of insulin-like growth factor-I mRNA in rat skeletal muscle

1989 ◽  
Vol 120 (1) ◽  
pp. 107-112 ◽  
Author(s):  
J. Isgaard ◽  
A. Nilsson ◽  
K. Vikman ◽  
O. G. P. Isaksson
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Rat Heart ◽  
Insulin Like Growth Factor ◽  
Rat Skeletal Muscle ◽  
Maximum Increase ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Dose Dependent

ABSTRACT Levels of mRNA for the insulin-like growth factor-I (IGF-I) in rat heart and skeletal muscle and its dependence on GH were investigated using a solution hybridization assay. Levels of IGF-I mRNA decreased following hypophysectomy, and replacement therapy with human GH (hGH) normalized heart and skeletal muscle levels. The stimulatory effect of hGH was dose-dependent, the lowest effective dose being 100 μg. A significant increase of IGF-I mRNA was observed 60 min after s.c. administration of 100 μg hGH and the maximum increase was apparent 6–12 h after hGH injection. Administration of 200 μg IGF-I or 11 μg insulin did not significantly change levels of IGF-I mRNA. The results show that GH regulates the level of IGF-I mRNA in rat heart and skeletal muscle and give further support to the hypothesis that locally produced IGF-I might be a local mediator for the direct stimulatory effect of GH on the growth and development of heart and skeletal muscle. Journal of Endocrinology (1989) 120, 107–112

Sign in / Sign up

Export Citation Format

Share Document