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.

O-Mannosylation of recombinant human insulin-like growth factor I (IGF-I) produced inSaccharomyces cerevisiae

FEBS Letters ◽  
1989 ◽  
Vol 248 (1-2) ◽  
pp. 111-114 ◽  
Author(s):  
Karl Hård ◽  
Wilbert Bitter ◽  
Johannis P. Kamerling ◽  
Johannes F.G. Vliegenthart
Keyword(s):  
Growth Factor ◽  
Human Insulin ◽  
Insulin Like Growth Factor ◽  
Recombinant Human Insulin ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

scholarly journals Effects of Recombinant Human Insulin-Like Growth Factor I Administration on Spontaneous and Growth Hormone (GH)-Releasing Hormone-Stimulated GH Secretion in Anorexia Nervosa1

2000 ◽  
Vol 85 (8) ◽  
pp. 2805-2809
Author(s):  
Laura Gianotti ◽  
Angela I. Pincelli ◽  
Massimo Scacchi ◽  
Mimma Rolla ◽  
Deanna Bellitti ◽  
...  
Keyword(s):  
Growth Factor ◽  
Normal Weight ◽  
Insulin Like Growth Factor ◽  
Recombinant Human Insulin ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Igfbp 3

Exaggerated GH and reduced insulin-like growth factor I (IGF-I) levels are common features in anorexia nervosa (AN). A reduction of the negative IGF-I feedback could account, in part, for GH hypersecretion. To ascertain this, we studied the effects of recombinant human (rh)IGF-I on spontaneous and GH-releasing hormone (GHRH)-stimulated GH secretion in nine women with AN [body mass index, 14.1 ± 0.6 kg/m2] and in weight matched controls (normal weight). Mean basal GH concentrations (mGHc) and GHRH (2.0μ g/kg, iv) stimulation were significantly higher in AN. rhIGF-I administration (20 μg/kg, sc) significantly reduced mGHc in AN (P &lt; 0.01), but not normal weight, and inhibited peak GH response to GHRH in both groups; mGHc and peak GH, however, persisted at a significantly higher level in AN. Insulin, glucose, and IGFBP-1 basal levels were similar in both groups. rhIGF-I inhibited insulin in AN, whereas glucose remained unaffected in both groups. IGFBP-1 increased in both groups (P &lt; 0.05), with significantly higher levels in AN. IGFBP-3 was under basal conditions at a lower level in AN (P &lt; 0.05) and remained unaffected by rhIGF-I. This study demonstrates that a low rhIGF-I dose inhibits, but does not normalize, spontaneous and GHRH-stimulated GH secretion in AN, pointing also to the existence of a defective hypothalamic control of GH release. Moreover, the increased IGFBP-1 levels might curtail the negative IGF-I feedback in AN.

scholarly journals Effects of Recombinant Human Insulin-Like Growth Factor I Administration on Growth Hormone (GH) Secretion, Both Spontaneous and Stimulated by GH-Releasing Hormone or Hexarelin, a Peptidyl GH Secretagogue, in Humans1

1999 ◽  
Vol 84 (1) ◽  
pp. 285-290
Author(s):  
E. Ghigo ◽  
L. Gianotti ◽  
E. Arvat ◽  
J. Ramunni ◽  
M. R. Valetto ◽  
...  
Keyword(s):  
Growth Factor ◽  
Negative Feedback ◽  
Inhibitory Effect ◽  
Insulin Like Growth Factor ◽  
Recombinant Human Insulin ◽  
Gh Secretion ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Hypothalamic Level

The negative feedback exerted by insulin-like growth factor I (IGF-I) on GH secretion occurs at the pituitary, as well as the hypothalamic level, via stimulation of SS and/or inhibition of GHRH release. In fact, recombinant human IGF-I (rhIGF-I) administration inhibits basal GH secretion, at least in fasted humans, though its effect on the GH response to GHRH is still controversial. GH secretagogues (GHS) are peptidyl and nonpeptidyl molecules that act on specific receptors at the pituitary and/or the hypothalamic level. Contrary to GHRH, the GH-releasing activity of GHS is strong, reproducible, and even partially refractory to inhibitory influences such as exogenous somatostatin. We studied the effects of rhIGF-I administration (20μ g/kg sc at 0 min) on GH secretion, either spontaneous or stimulated by GHRH (2 μg/kg iv at +180 min) or Hexarelin (HEX, 2.0 μg/kg iv at+ 180 min), a GHS, in eight normal young women (age, mean ± sem, 28.3 ± 1.2 yr; body mass index, 20.1± 0.5 kg/m2). rhIGF-I administration increased IGF-I levels (peak vs. baseline: 420.3 ± 30.5 vs. 274.4 ± 25.3 μg/L, P &lt; 0.05) within the physiological range from +120 to +300 min. No variation in glucose or insulin levels was recorded. rhIGF-I did not reduce spontaneous GH secretion [areas under curves (AUC)0–300 min 140.6± 66.3 vs. 114.6 ± 32.1 μg/L·h], whereas it inhibited the GH response to both GHRH (AUC180–300 min 447.7 ± 159.4 vs. 715.9 ± 104.3 μg/L·h, P &lt; 0.05) and HEX (620.3 ± 110.4 vs. 1705.9 ± 328.9 μg/L·h, P &lt; 0.03). The percent inhibitory effect of rhIGF-I on the GH response to GHRH (41.7 ± 12.8%) was lower than that on the response to HEX (57.7 ± 11.0%). In fact, the GH response to GHRH alone was clearly lower than that to HEX alone (P &lt; 0.05), whereas the GH responses to GHRH and HEX were similar after rhIGF-I. Our findings show that the sc administration of low rhIGF-I doses inhibits the GH response to GHRH and, even more, that to HEX; whereas, at least in this experimental design in fed conditions, it does not modify the spontaneous GH secretion. Because GHS generally show partial refractoriness to inhibitory inputs, including exogenous somatostatin, the present results point toward a peculiar sensitivity of GHS to the negative feedback action of IGF-I.

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.

Effects of dietary recombinant human insulin-like growth factor-I on concentrations of hormones and growth factors in the blood of newborn calves

1994 ◽  
Vol 140 (1) ◽  
pp. 15-21 ◽  
Author(s):  
C R Baumrucker ◽  
J W Blum
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Milk Replacer ◽  
Insulin Like Growth Factor ◽  
Recombinant Human Insulin ◽  
Blood Concentrations ◽  
Factor I ◽  
First Feeding ◽  
Igf I ◽  
Growth Factor I

Abstract Colostrum is rich in insulin-like growth factor-I (IGF-I) and IGF-II and the dietary effects of recombinant human IGF-I (rhIGF-I) on the newborn are of interest. The objective of this study was to examine the effects of dietary rhIGF-I upon selected hormones and growth factors in the blood. Calves were fed for the first 2 days of life with one of three experimental diets: (1) milk replacer plus isolated colostrum-derived globulin (MR−), (2) as (1) plus 98 μmol rhIGF-I/l (MR+) or (3) pooled cow colostrum. Thereafter, all animals received only milk replacer at 5% of body weight/feeding twice a day with only treatment 2 having the continued addition of 98 μmol rhIGF-I/l until completion of the experiment 7 days after birth. Radioimmunoassays for insulin, prolactin, IGF-I, IGF-II, GH, l-thyroxine, 3,5,3′-l-triiodothyroline and cortisol were conducted. With the exception of GH, all hormones and growth factors examined showed some form of dietary effect, but many were transient, changing only with the first feeding. Both insulin and prolactin concentrations exhibited a transient increase in blood at the first feeding, but insulin increased with the MR− treatment whereas prolactin increased with the MR+ treatment. Total IGF-I concentration in blood did not show any diet-induced changes for the first 4 days, but thereafter a rise in blood concentrations of IGF-I was observed. These data indirectly support the hypothesis that dietary IGF-I may be absorbed and causes transient systemic effects in the newborn calf. Journal of Endocrinology (1994) 140, 15–21

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