Acute effects of insulin-like growth factor-I (IGF-I) on bone protein synthesis in rats

1994 ◽  
Vol 1199 (1) ◽  
pp. 101-103 ◽  
Author(s):  
Alfredo J. Martínez ◽  
Mónica Pascual ◽  
Jesús Larralde
Keyword(s):  
Protein Synthesis ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Acute Effects ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

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.

Effects of insulin-like growth factor-I, insulin, and leucine on protein turnover and ubiquitin ligase expression in rainbow trout primary myocytes

2010 ◽  
Vol 298 (2) ◽  
pp. R341-R350 ◽  
Author(s):  
Beth M. Cleveland ◽  
Gregory M. Weber
Keyword(s):  
Protein Synthesis ◽  
Rainbow Trout ◽  
Growth Factor ◽  
Protein Degradation ◽  
Ubiquitin Ligase ◽  
Protein Turnover ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

The effects of insulin-like growth factor-I (IGF-I), insulin, and leucine on protein turnover and pathways that regulate proteolytic gene expression and protein polyubiquitination were investigated in primary cultures of 4-day-old rainbow trout myocytes. Supplementing media with 100 nM IGF-I increased protein synthesis by 13% ( P < 0.05) and decreased protein degradation by 14% ( P < 0.05). Treatment with 1 μM insulin increased protein synthesis by 13% ( P < 0.05) and decreased protein degradation by 17% ( P < 0.05). Supplementing media containing 0.6 mM leucine with an additional 2.5 mM leucine did not increase protein synthesis rates but reduced rates of protein degradation by 8% ( P < 0.05). IGF-I (1 nM–100 nM) and insulin (1 nM-1 μM) independently reduced the abundance of ubiquitin ligase mRNA in a dose-dependent manner, with maximal reductions of ∼70% for muscle atrophy F-box (Fbx) 32, 40% for Fbx25, and 25% for muscle RING finger-1 (MuRF1, P < 0.05). IGF-I and insulin stimulated phosphorylation of FOXO1 and FOXO4 ( P < 0.05), which was inhibited by the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin, and decreased the abundance of polyubiquitinated proteins by 10–20% ( P < 0.05). Supplementing media with leucine reduced Fbx32 expression by 25% ( P < 0.05) but did not affect Fbx25 nor MuRF1 transcript abundance. Serum deprivation decreased rates of protein synthesis by 60% ( P < 0.05), increased protein degradation by 40% ( P < 0.05), and increased expression of all ubiquitin ligases. These data suggest that, similar to mammals, the inhibitory effects of IGF-I and insulin on proteolysis occur via P I3-kinase/protein kinase B signaling and are partially responsible for the ability of these compounds to promote protein accretion.

Increase in tendon protein synthesis in response to insulin-like growth factor-I is preserved in elderly men

2014 ◽  
Vol 116 (1) ◽  
pp. 42-46 ◽  
Author(s):  
Rie Harboe Nielsen ◽  
Lars Holm ◽  
Nikolaj Mølkjær Malmgaard-Clausen ◽  
Søren Reitelseder ◽  
Katja Maria Heinemeier ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Growth Factor ◽  
Age Groups ◽  
Synthesis Rate ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Old Men

Insulin-like growth factor-I (IGF-I) is known to be an anabolic factor in tendon, and the systemic levels are reduced with aging. However, it is uncertain how tendon fibroblasts are involved in tendon aging and how aging cells respond to IGF-I. The purpose of this study was to investigate the in vivo IGF-I stimulation of tendon protein synthesis in elderly compared with young men. We injected IGF-I in the patellar tendons of young ( n = 11, 20–30 yr of age) and old ( n = 11, 66–75 yr of age) men, and the acute fractional synthesis rate (FSR) of tendon protein was measured with the stable isotope technique and compared with the contralateral side (injected with saline as control). We found that tendons injected with IGF-I had significantly higher protein FSR compared with controls (old group: 0.018 ± 0.015 vs. 0.008 ± 0.008, young group: 0.016 ± 0.009 vs. 0.009 ± 0.006%/h, mean ± SE, P < 0.01). This increase in protein synthesis was seen in both young and old men, with no differences between age groups. The old group had markedly lower serum IGF-I levels compared with young (165 ± 17 vs. 281 ± 27 ng/ml, P < 0.01). In conclusion, local IGF-I stimulated tendon protein synthesis in both young and old men, despite lower systemic IGF-I levels in the old group. This could indicate that the changed phenotype in aging tendon is not caused by decreased fibroblast function.

Tendon protein synthesis rate in classic Ehlers-Danlos patients can be stimulated with insulin-like growth factor-I

2014 ◽  
Vol 117 (7) ◽  
pp. 694-698 ◽  
Author(s):  
Rie Harboe Nielsen ◽  
Lars Holm ◽  
Jacob Kildevang Jensen ◽  
Katja Maria Heinemeier ◽  
Lars Remvig ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Growth Factor ◽  
Connective Tissue ◽  
Patellar Tendon ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

The classic form of Ehlers-Danlos syndrome (cEDS) is an inherited connective tissue disorder, where mutations in type V collagen-encoding genes result in abnormal collagen fibrils. Thus the cEDS patients have pathological connective tissue morphology and low stiffness, but the rate of connective tissue protein turnover is unknown. We investigated whether cEDS affected the protein synthesis rate in skin and tendon, and whether this could be stimulated in tendon tissue with insulin-like growth factor-I (IGF-I). Five patients with cEDS and 10 healthy, matched controls (CTRL) were included. One patellar tendon of each participant was injected with 0.1 ml IGF-I (Increlex, Ipsen, 10 mg/ml) and the contralateral tendon with 0.1 ml isotonic saline as control. The injections were performed at both 24 and 6 h prior to tissue sampling. The fractional synthesis rate (FSR) of proteins in skin and tendon was measured with the stable isotope technique using a flood-primed continuous infusion over 6 h. After the infusion one skin biopsy and two tendon biopsies (one from each patellar tendon) were obtained. We found similar baseline FSR values in skin and tendon in the cEDS patients and controls [skin: 0.005 ± 0.002 (cEDS) and 0.007 ± 0.002 (CTRL); tendon: 0.008 ± 0.001 (cEDS) and 0.009 ± 0.002 (CTRL) %/h, mean ± SE]. IGF-I injections significantly increased FSR values in cEDS patients but not in controls (delta values: cEDS 0.007 ± 0.002, CTRL 0.001 ± 0.001%/h). In conclusion, baseline protein synthesis rates in connective tissue appeared normal in cEDS patients, and the patients responded with an increased tendon protein synthesis rate to IGF-I injections.

scholarly journals Restoration of insulin-like growth factor I action in skeletal muscle of old mice

1998 ◽  
Vol 275 (3) ◽  
pp. E525-E530 ◽  
Author(s):  
P. E. Willis ◽  
S. G. Chadan ◽  
V. Baracos ◽  
W. S. Parkhouse
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Growth Factor ◽  
Protein Content ◽  
Receptor Protein ◽  
Insulin Like Growth Factor ◽  
Chronic Exercise ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

This study examined the effects of long-term chronic voluntary wheel exercise on the ability of insulin-like growth factor I (IGF-I) to stimulate rates of protein synthesis in the soleus muscle of old C57Bl/6 mice. Factors contributing to any changes in hormone action were analyzed at the level of hormone receptor binding, protein content, and gene expression. Chronic exercise resulted in an increased skeletal muscle mass (10–22%) and a 56% increase in IGF-I-stimulated rates of protein synthesis ( P < 0.05). IGF-I receptor mRNA was increased 46%, IGF-Ireceptor protein was increased 65%, and the binding capacity of the IGF-I high-affinity site was increased sixfold ( P < 0.05) with chronic wheel exercise. Insulin receptor protein content was decreased 35% ( P < 0.05), whereas GLUT-4 content was increased 47% with chronic exercise ( P < 0.05). This study demonstrates that old animals retain a plasticity for IGF I receptor and glucose transporter expression that may have valuable physiological consequences.

scholarly journals Insulin-like Growth Factor I (IGF-I) Increases Whole Body Protein Synthesis in Contrast to Insulin Which Reduces Proteolysis

1994 ◽  
Vol 3 (Supple5) ◽  
pp. 240-240
Author(s):  
David L. Russell-Jones ◽  
Marlot A. Umpleby ◽  
Tom D. Hennessy ◽  
Peter H. Sonksen
Keyword(s):  
Protein Synthesis ◽  
Growth Factor ◽  
Whole Body ◽  
Insulin Like Growth Factor ◽  
Body Protein ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Insulin-like growth factor I stimulates Na-dependent Pi transport in cultured kidney cells

1989 ◽  
Vol 257 (5) ◽  
pp. F712-F717 ◽  
Author(s):  
J. Caverzasio ◽  
J. P. Bonjour
Keyword(s):  
Protein Synthesis ◽  
Growth Factor ◽  
De Novo ◽  
Maximal Response ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Pi Transport ◽  
Igf I ◽  
Growth Factor I ◽  
Stimulation Of

The effect of recombinant insulin-like growth factor I (IGF-I/somatomedin C) on the transport of inorganic phosphate (Pi) was studied in cultured kidney epithelia. In opossum kidney (OK) epithelia, IGF-I (5 x 10(-10) to 10(-7) M) induced a dose-related stimulation of the Na-dependent Pi transport (NaPiT). A maximal response was observed at 10(-7) M (IGF-I 1.64 +/- 0.12; vehicle 0.90 +/- 0.02 nmol.mg protein-1. 4 min-1, P less than 0.001). Kinetic analysis of the stimulatory effect of IGF-I on NaPiT indicated an increase in Vmax and no change in Km. Insulin also stimulated NaPiT in OK epithelia but only at concentrations 20-40 times higher than IGF-I. The effect of IGF-I on Pi transport was detectable in less than 30 min with a maximal response occurring after 4-5 h. It was selective for NaPiT, since the Na-dependent alanine transport was not affected by IGF-I. Inhibition of protein synthesis by either cycloheximide or cordycepin markedly attenuated the stimulatory effect of IGF-I on NaPiT. The cellular adenosine 3',5'-cyclic monophosphate content was not modified by the growth factor. In conclusion, these data indicate that IGF-I increases NaPiT selectively through a mechanism that involves de novo protein synthesis. These observations suggest that growth and growth hormone-related stimulation of renal Pi transport could be mediated by IGF-I.

scholarly journals Time- and Dose-Related Interactions between Glucocorticoid and Cyclic Adenosine 3′,5′-Monophosphate on CCAAT/Enhancer-Binding Protein-Dependent Insulin-Like Growth Factor I Expression by Osteoblasts1

Endocrinology ◽  
2000 ◽  
Vol 141 (1) ◽  
pp. 127-137 ◽  
Author(s):  
Thomas L. McCarthy ◽  
Changhua Ji ◽  
Yun Chen ◽  
Kenneth Kim ◽  
Michael Centrella
Keyword(s):  
Protein Synthesis ◽  
Growth Factor ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Enhancer Binding Protein ◽  
Igf I ◽  
Ccaat Enhancer Binding Protein ◽  
Growth Factor I ◽  
I Gene

Abstract Glucocorticoid has complex effects on osteoblasts. Several of these changes appear to be related to steroid concentration, duration of exposure, or specific effects on growth factor expression or activity within bone. One important bone growth factor, insulin-like growth factor I (IGF-I), is induced in osteoblasts by hormones such as PGE2 that increase intracellular cAMP levels. In this way, PGE2 activates transcription factor CCAAT/enhancer-binding protein-δ (C/EBPδ) and enhances its binding to a specific control element found in exon 1 in the IGF-I gene. Our current studies show that preexposure to glucocorticoid enhanced C/EBPδ and C/EBPβ expression by osteoblasts and thereby potentiated IGF-I gene promoter activation in response to PGE2. Importantly, this directly contrasts with inhibitory effects on IGF-I expression that result from sustained or pharmacologically high levels of glucocorticoid exposure. Consistent with the stimulatory effect of IGF-I on bone protein synthesis, pretreatment with glucocorticoid sensitized osteoblasts to PGE2, and in this context significantly enhanced new collagen and noncollagen protein synthesis. Therefore, pharmacological levels of glucocorticoid may reduce IGF-I expression by osteoblasts and cause osteopenic disease, whereas physiological transient increases in glucocorticoid may permit or amplify the effectiveness of hormones that regulate skeletal tissue integrity. These events appear to converge on the important role of C/EBPδ and C/EBPβ on IGF-I expression by osteoblasts.

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