Enhanced response of muscle protein synthesis and plasma insulin to food intake in suckled rats

1993 ◽  
Vol 265 (2) ◽  
pp. R334-R340 ◽  
Author(s):  
T. A. Davis ◽  
M. L. Fiorotto ◽  
H. V. Nguyen ◽  
P. J. Reeds
Keyword(s):  
Protein Synthesis ◽  
Food Intake ◽  
Plasma Insulin ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Fed State ◽  
Fasting And Refeeding ◽  
Old Rats ◽  
Amino Acid Concentrations

To compare the sensitivity of muscle protein synthesis to food intake in neonatal and weaned rats, 5- and 16-day-old suckled rats and 28-day-old weaned rats were either fed, fasted for 8-10 h, or refed for 1-4 h after an 8-h fast. Protein synthesis was measured in vivo in soleus and plantaris muscles with a large dose of L-[4-3H]phenylalanine. In fed rats, fractional rates of protein synthesis (KS) decreased with age. Fasting decreased KS, and refeeding increased KS most in 5-day-old animals, less in 16-day-old rats, and least in 28-day-old rats. In 5-day-old rats, there were no differences in KS between soleus and plantaris muscles in the fed state and after fasting and refeeding; at 28 days, KS was higher in soleus than in plantaris in fed rats, and the soleus did not respond to fasting and refeeding. In rats at all three ages, the concentration of most plasma amino acids decreased during fasting; when 5-day-old rats were refed, plasma amino acid concentrations increased, but not to the levels in the fed state. Plasma insulin concentrations increased with age. Plasma insulin concentrations decreased more rapidly with fasting and increased more extensively with refeeding in 5-day-old rats than in older rats. These results suggest that muscle protein synthesis is more responsive to food intake in young suckled rats than in older suckled or weaned rats; this increased responsiveness is accompanied by greater changes in circulating insulin concentrations.

Adaptation to prolonged starvation in the rat: curtailment of skeletal muscle proteolysis

1981 ◽  
Vol 241 (4) ◽  
pp. E321-E327 ◽  
Author(s):  
M. N. Goodman ◽  
M. A. McElaney ◽  
N. B. Ruderman
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Early Event ◽  
Body Protein ◽  
Fed State ◽  
Prolonged Starvation ◽  
Obese Rats ◽  
Old Rats

Previous studies have established that 16-wk-old nonobese and obese rats conserve body protein during prolonged starvation. To determine the basis for this, protein synthesis and degradation in skeletal muscle were evaluated in the isolated perfused hindquarters of these rats, in the fed state and when starved for 2, 5, 10, and 11 days. Rats aged 4 and 8 wk were used as a comparison. The results indicate that the response to starvation depends on several factors: the age of the rat, its degree of adiposity, and the duration of the fast. An early event in starvation was a decline in muscle protein synthesis. This occurred in all groups, albeit this reduction occurred more slowly in the older rats. A later response to starvation was an increase in muscle proteolysis. This occurred between 2 and 5 days in the 8-wk-old rats. In 16-wk-old rats it did not occur until between 5 and 10 days, and it was preceded by a period of decreased proteolysis. In 16-wk-old obese rats, a decrease in proteolysis persisted for upwards of 10 days and the secondary increase was not noted during the period of study. The data suggest that the ability of older and more obese rats to conserve body protein during starvation is due, in part, to a curtailment of muscle proteolysis. This adaptation seems to correlate with the availability of lipid fuels.

IGF-I stimulation of muscle protein synthesis in the awake rat: permissive role of insulin and amino acids

1996 ◽  
Vol 270 (1) ◽  
pp. E60-E66 ◽  
Author(s):  
R. Jacob ◽  
X. Hu ◽  
D. Niederstock ◽  
S. Hasan ◽  
P. H. McNulty ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Plasma Insulin ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Amino Acid Replacement ◽  
Igf I ◽  
Awake Rat

Infusion of insulin-like growth factor I (IGF-I) lowers plasma amino acid and insulin concentrations, which may limit the capacity of IGF-I to promote muscle protein synthesis in vivo. We measured heart and skeletal muscle incorporation of continuously infused L-[ring-2,6-3H]phenylalanine in awake postabsorptive rats receiving 4-h intravenous infusions of saline (n = 11), IGF-I (1 microgram.kg-1.min-1) with (n = 10) or without (n = 11) amino acid replacement, or IGF-I with insulin replacement (n = 8). There were no significant increases in muscle protein synthesis during the infusion of IGF-I alone, which was associated with decreases in both plasma insulin (52 +/- 5%, P < 0.001) and amino acids (25 +/- 5%, P < 0.05). When IGF-I was given together with amino acids, protein synthesis was significantly increased in gastrocnemius (4.7 +/- 0.4 vs. 2.5 +/- 0.3%/day, P < 0.001), oblique (4.5 +/- 0.4 vs. 2.8 +/- 0.4%/day, P < 0.05), and soleus (8.8 +/- 0.7 vs. 6.4 +/- 0.3%/day, P < 0.01) and tended to be higher than saline control values in heart (10.9 +/- 0.9 vs. 8.8 +/- 0.7%/day, P = 0.08). Amino acid replacement prevented plasma concentrations from falling and also blunted the decline in plasma insulin (22 +/- 5%, P < 0.01 vs. IGF-I alone). When IGF-I and insulin replacement were given, protein synthesis was increased in heart (13.0 +/- 0.6%/day), gastrocnemius (4.7 +/- 0.4%/day), and oblique (4.5 +/- 0.4%/day) (P < 0.001 for each, compared with saline). We conclude that the action of IGF-I to acutely stimulate muscle protein synthesis in the awake rat is limited by the fall in circulating insulin and/or amino acid concentrations that accompanies IGF-I infusion in vivo and is prevented by co-infusion of insulin or amino acids.

scholarly journals The effect of insulin infusion and food intake on muscle protein synthesis in postabsorptive rats

1983 ◽  
Vol 210 (3) ◽  
pp. 669-676 ◽  
Author(s):  
P J Garlick ◽  
M Fern ◽  
V R Preedy
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Food Intake ◽  
Plasma Insulin ◽  
Insulin Infusion ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Young Male ◽  
Male Rats ◽  
Significant Stimulation

1. Insulin was infused into young male rats in the postabsorptive state. Rates of protein synthesis in skeletal muscle were determined during the final 10 min of infusion from the incorporation of label into protein after intravenous injection of a massive dose of [3H]phenylalanine. Rates of synthesis were not altered during the first 10 min of insulin infusion, but were increased significantly between 10 and 60 min. 2. Rats were infused with different amounts of insulin for 30 min. When concentrations were increased from 10 to 40 microunits/ml of plasma there was no change in muscle protein synthesis, but concentrations higher than 70 microunits/ml caused a significant stimulation. Concentrations below 10 microunits/ml, obtained by infusion of anti-insulin serum, did not depress synthesis below that found in the postabsorptive rat. 3. Infusion of glucose for 30 or 60 min led to an increase in plasma insulin to 40 microunits/ml, but this also failed to stimulate muscle protein synthesis. 4. Rates of synthesis in postabsorptive rats, even when stimulated maximally by insulin, were not so high as those in fed rats or in postabsorptive rats refed for 60 min. However, in fed and refed rats insulin concentrations were below that required to stimulate synthesis in postabsorptive animals. Despite this, infusion of large amounts of insulin into fed rats did not increase synthesis further. 5. The sensitivity of plasma glucose to insulin infusion was different from that of protein synthesis. A decrease in glucose concentration preceded the increase in synthesis and occurred at lower insulin concentrations. 6. It is concluded that changes in circulating insulin may have been partly responsible for the increase in muscle protein synthesis brought about by feeding, but that other factors must also play a part.

scholarly journals The relative importance of muscle protein synthesis and breakdown in the regulation of muscle mass

1976 ◽  
Vol 156 (1) ◽  
pp. 185-188 ◽  
Author(s):  
D J Millward ◽  
P J Garlick ◽  
D O Nnanyelugo ◽  
J C Waterlow
Keyword(s):  
Protein Synthesis ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Relative Importance ◽  
Protein Breakdown ◽  
Protein Mass ◽  
Branched Chain ◽  
Amino Acid Concentrations

The effects of growth-suppressing and muscle-wasting treatments on muscle protein turnover and amino acid concentrations were determined in vivo. All treatments depressed protein synthesis and some treatments depressed protein breakdown. Only prolonged starvation increased protein breakdown. Muscle protein mass is regulated primarily through alterations in protein synthesis in all except emergency conditions. The increased concentrations of the branched-chain amino acids indicate that they are unlikely to be involved in this regulation.

scholarly journals The effect of glucagon administration on protein synthesis in skeletal muscles, heart and liver in vivo

1985 ◽  
Vol 228 (3) ◽  
pp. 575-581 ◽  
Author(s):  
V R Preedy ◽  
P J Garlick
Keyword(s):  
Protein Synthesis ◽  
Skeletal Muscles ◽  
Plasma Insulin ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Diabetic Rats ◽  
Liver Protein ◽  
Food Absorption ◽  
Metabolic Stresses

Infusion of glucagon (0.5 mg/h per 100 g body wt.) into fed rats for 6 h inhibited protein synthesis in skeletal muscle, but not in heart. The order of sensitivity of three muscles was plantaris greater than gastrocnemius greater than soleus. Treatment with glucagon for periods of 1 h or less had no effect. Liver protein synthesis was inhibited by glucagon treatment for 10 min, but stimulated after 6 h. The effect of glucagon on muscle was not secondary to impaired food absorption or to depletion of amino acids by increased gluconeogenesis, since the inhibition of protein synthesis was observed in postabsorptive and amino acid-infused rats. The failure of glucagon to inhibit muscle protein synthesis after 1 h may have been caused by the increase in plasma insulin that occurred at this time, since an inhibition was detected in insulin-treated diabetic rats. The lowest infusion rate that gave a significant decrease in muscle protein synthesis was 6 micrograms/h per 100 g body wt., despite a small increase in plasma insulin. This gave plasma glucagon concentrations in the high pathophysiological range, suggesting that glucagon may be significant in the pathogenesis of muscle wasting in metabolic stresses such as diabetes and starvation.

Chronic effects of β2 agonists on body composition and protein synthesis in the rat

1984 ◽  
Vol 4 (1) ◽  
pp. 83-91 ◽  
Author(s):  
P. W. Emery ◽  
N. J. Rothwell ◽  
M. J. Stock ◽  
P. D. Winter
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Binding Capacity ◽  
Body Weight Gain ◽  
Muscle Protein Synthesis ◽  
Body Protein ◽  
Fractional Rate ◽  
Brown Adipose ◽  
Β2 Agonists

Chronic treatment of rats with the β2-adrenergic agonists clenbuterol and fenoterol over 16–19 d raised energy intake, expenditure, and body weight gain but did not affect fat or energy deposition, and body protein gain was increased by 50 and 18%, respectively. Both drugs increased the protein content and mitochondrial GDP-binding capacity of brown adipose tissue. Clenbuterol did not affect plasma insulin, growth hormone, or triiodothyronine levels, although insulin levels were reduced by fenoterol. Both drugs caused hypertrophy of skeletal muscle (gastrocnemius), and muscle protein synthesis in vivo (fractional rate) was elevated by 34 and 26% in clenbuterol and fenoteroltreated rats, respectively.

scholarly journals Proteasome- and Calpain-Mediated Proteolysis, but Not Autophagy, Is Required for Leucine-Induced Protein Synthesis in C2C12 Myotubes

Physiologia ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 22-33
Author(s):  
Shelby C. Osburn ◽  
Christopher G. Vann ◽  
David D. Church ◽  
Arny A. Ferrando ◽  
Michael D. Roberts
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Proteasome Inhibition ◽  
Coupled Processes ◽  
C2c12 Myotubes ◽  
Calpain Inhibitor ◽  
Tightly Coupled

Muscle protein synthesis and proteolysis are tightly coupled processes. Given that muscle growth is promoted by increases in net protein balance, it stands to reason that bolstering protein synthesis through amino acids while reducing or inhibiting proteolysis could be a synergistic strategy in enhancing anabolism. However, there is contradictory evidence suggesting that the proper functioning of proteolytic systems in muscle is required for homeostasis. To add clarity to this issue, we sought to determine if inhibiting different proteolytic systems in C2C12 myotubes in conjunction with acute and chronic leucine treatments affected markers of anabolism. In Experiment 1, myotubes underwent 1-h, 6-h, and 24-h treatments with serum and leucine-free DMEM containing the following compounds (n = 6 wells per treatment): (i) DMSO vehicle (CTL), (ii) 2 mM leucine + vehicle (Leu-only), (iii) 2 mM leucine + 40 μM MG132 (20S proteasome inhibitor) (Leu + MG132), (iv) 2 mM leucine + 50 μM calpeptin (calpain inhibitor) (Leu + CALP), and (v) 2 mM leucine + 1 μM 3-methyladenine (autophagy inhibitor) (Leu + 3MA). Protein synthesis levels significantly increased (p < 0.05) in the Leu-only and Leu + 3MA 6-h treatments compared to CTL, and levels were significantly lower in Leu + MG132 and Leu + CALP versus Leu-only and CTL. With 24-h treatments, total protein yield was significantly lower in Leu + MG132 cells versus other treatments. Additionally, the intracellular essential amino acid (EAA) pool was significantly greater in 24-h Leu + MG132 treatments versus other treatments. In a follow-up experiment, myotubes were treated for 48 h with CTL, Leu-only, and Leu + MG132 for morphological assessments. Results indicated Leu + MG132 yielded significantly smaller myotubes compared to CTL and Leu-only. Our data are limited in scope due to the utilization of select proteolysis inhibitors. However, this is the first evidence to suggest proteasome and calpain inhibition with MG132 and CALP, respectively, abrogate leucine-induced protein synthesis in myotubes. Additionally, longer-term Leu + MG132 treatments translated to an atrophy phenotype. Whether or not proteasome inhibition in vivo reduces leucine- or EAA-induced anabolism remains to be determined.

Measurement of the Rate of Protein Synthesis in Muscle of Postabsorptive Young Men by Injection of a ‘Flooding Dose’ of [1-13C]leucine

1989 ◽  
Vol 77 (3) ◽  
pp. 329-336 ◽  
Author(s):  
Peter J. Garlick ◽  
Jan Wernerman ◽  
Margaret A. McNurlan ◽  
Pia Essen ◽  
Gerald E. Lobley ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Isotopic Enrichment ◽  
Plasma Leucine ◽  
Convenient Technique ◽  
Tissue Compartments ◽  
Muscle Biopsies

1. The ‘flooding dose’ technique for measuring the rate of protein synthesis in tissues in vivo involves the injection of a large amount of unlabelled amino acid together with the tracer to minimize differences in isotopic enrichment of the free amino acid in plasma and tissue compartments. This approach has been investigated in human muscle by taking biopsies from postabsorptive male volunteers given [1-13C]leucine. 2. Intravenous injection of 4 g of unlabelled leucine resulted in a rapid rise in free leucine concentration of seven- to eleven-fold in plasma and five-fold in muscle. Values were still elevated by two-fold after 2 h. 3. Five minutes after injection of [1-13C]leucine (0.05 g/kg) the isotopic enrichment of plasma leucine was 82% that of the injected material, falling to 44% at 120 min. The enrichment of free leucine in sequential muscle biopsies was close to that in plasma and almost identical to that for plasma α-ketoisocaproate. 4. The rate of protein synthesis was determined from the increase in leucine enrichment in protein of muscle biopsies taken before and 90 min after injection of [1-13C]leucine (0.05 g/kg; 19 or 39 atom% excess) and the average plasma α-ketoisocaproate enrichment over this period (taken to represent muscle free leucine). The mean rate of muscle protein synthesis in 10 subjects was 1.95 (sem 0.12)%/day. Rates of protein synthesis calculated from plasma leucine as precursor enrichment were only 5% lower than those calculated from plasma α-ketoisocaproate. 5. It is concluded that a ‘flooding dose’ of 13C-labelled amino acid is a useful and convenient technique for determining the rate of protein synthesis in tissues of human volunteers and patients.

Effects of food deprivation on protein synthesis and degradation in rat skeletal muscles

1976 ◽  
Vol 231 (2) ◽  
pp. 441-448 ◽  
Author(s):  
JB Li ◽  
AL Goldberg
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Food Deprivation ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Rna Content ◽  
Fasted Rats ◽  
Synthesis And Degradation

The effects of food deprivation on protein turnover in rat soleus and extensor digitorum longus (EDL) were investigated. Muscles were removed from fed or fasted growing rats, and protein synthesis and breakdown were measured during incubation in vitro. Rates of synthesis and degradation were higher in the dark soleus than in the pale EDL. One day after food removal protein synthesis and RNA content in the EDL decreased. On the 2nd day of fasting, rates of protein catabolism in this muscle increased. Little or no change in synthesis and degradation occurred in the soleus. Consequently, during fasting the soleus lost much less weight than the EDL and other rat muscles. In unsupplemented buffer or in medium containing amino acids, glucose, and insulin, the muscles of fasted rats showed a lower rate of protein synthesis expressed per milligram of tissue but not per microgram of RNA. Thus the decrease in muscle RNA on fasting was responsible for the reduced synthesis observed under controlled in vitro conditions. In vivo the reduction in muscle protein synthesis on fasting results both from a lower RNA content and lower rate of synthesis per microgram of RNA. Reduced supply of glucose, insulin, and amino acids may account for the lower rate of synthesis per microgram of RNA demonstrable in vivo.

scholarly journals Glucocorticoid effects on insulin- and IGF-I-regulated muscle protein metabolism during aging

1998 ◽  
Vol 156 (1) ◽  
pp. 83-89 ◽  
Author(s):  
D Dardevet ◽  
C Sornet ◽  
I Savary ◽  
E Debras ◽  
P Patureau-Mirand ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Atrophy ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Recovery Period ◽  
Adult Rats ◽  
Igf I ◽  
Muscle Protein Metabolism ◽  
Old Rats

This study was performed to assess the effect of glucocorticoids (dexamethasone) on insulin- and IGF-I-regulated muscle protein metabolism in adult and old rats. Muscle atrophy occurred more rapidly in old rats, and recovery of muscle mass was impaired when compared with adults. Muscle wasting resulted mainly from increased protein breakdown in adult rat but from depressed protein synthesis in the aged animal. Glucocorticoid treatment significantly decreased the stimulatory effect of insulin and IGF-I on muscle protein synthesis in adult rats by 25.9 and 58.1% respectively. In old rats, this effect was even greater, being 49.3 and 100% respectively. With regard to muscle proteolysis, glucocorticoids blunted the anti-proteolytic action of insulin and IGF-I in both age groups. During the recovery period, adult rats reversed the glucocorticoid-induced resistance of muscle protein metabolism within 3 days, at which time old rats still exhibited the decrease in insulin-regulated proteolysis. In conclusion, the higher sensitivity of old rat muscle to glucocorticoids may in part result from the greater modification of the effects of insulin and IGF-I on muscle protein metabolism. These responses to glucocorticoids in old rats may be associated with the emergence of muscle atrophy with advancing age.

Sign in / Sign up

Export Citation Format

Share Document