Interaction of amino acids and insulin in the regulation of protein metabolism in growing animals

2003 ◽  
Vol 83 (3) ◽  
pp. 357-364 ◽  
Author(s):  
T. A. Davis ◽  
A. Suryawan ◽  
J. A. Bush ◽  
P. M. J. O’Connor ◽  
M. C. Thivierge
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Intracellular Signaling ◽  
Intracellular Signaling Pathways ◽  
Dietary Amino Acids ◽  
Initiation Of Translation ◽  
Tissue Protein Synthesis ◽  
Key Words Muscle ◽  
Stimulation Of

Young animals utilize their dietary amino acids more efficiently for growth because they are capable of a greater increase in tissue protein synthesis in response to feeding than older animals. This response to feeding is particularly profound in skeletal muscle. The feeding-induced stimulation of protein synthesis in skeletal muscle is uniquely and independently regulated by both insulin and amino acids. In most visceral tissues, the stimulation of protein synthesis by feeding is mediated by amino acids alone and not by insulin. The stimulation of protein synthesis by nutrition and hormones is regulated by alterations in the expression and activity of components of the intracellular signaling pathways that control the initiation of translation. Key words: Muscle, pigs, neonate, protein synthesis, insulin, amino acids

Role of Amino Acids and Peptides in the Molecular Signaling in Skeletal Muscle after Resistance Exercise

2007 ◽  
Vol 17 (s1) ◽  
pp. S47-S57 ◽  
Author(s):  
René Koopman
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Resistance Exercise ◽  
Translation Initiation ◽  
Intracellular Signaling ◽  
Muscle Protein ◽  
Mrna Translation ◽  
Molecular Signaling ◽  
Stimulation Of

Resistance exercise can effectively result in an increase in muscle mass, or hypertrophy, which generally becomes apparent after several weeks of training. Muscle hypertrophy requires muscle protein synthesis to exceed protein breakdown during an extended time period. It has been firmly established that the interaction between exercise and nutrition (i.e., protein intake) is necessary to attain net protein accretion in skeletal muscle. The stimulation of protein synthesis is caused in part by stimulation of mRNA translation initiation. There is relatively little information on the response of intracellular signaling controlling mRNA translation to exercise and nutrition, especially in humans, but the available data in humans seem to suggest that a single bout of resistance exercise does not substantially enhance PI-3 kinase/mTOR signaling during the first 2 h after exercise. Moreover, it is demonstrated that the ingestion of protein or amino acids after exercise is crucial to further stimulate molecular signaling that controls translation initiation. The aim of this review is to provide an overview of the intracellular signaling related to translational control and to provide a summary of the current knowledge about the response of the signaling pathways controlling the anabolic response to exercise and nutrient intake in vivo in humans.

Protein synthesis in skeletal muscle and jejunum is more responsive to feeding in 7-than in 26-day-old pigs

1996 ◽  
Vol 270 (5) ◽  
pp. E802-E809 ◽  
Author(s):  
T. A. Davis ◽  
D. G. Burrin ◽  
M. L. Fiorotto ◽  
H. V. Nguyen
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Plasma Concentrations ◽  
Postnatal Life ◽  
Tissue Protein ◽  
Igf I ◽  
Tissue Protein Synthesis ◽  
Stimulation Of

The study aimed to determine the developmental changes in the response of peripheral and visceral tissue protein synthesis to feeding during early postnatal life and the associated changes in circulating insulin, insulin-like growth factor (IGF-I), and amino acid concentrations. Tissue protein synthesis was measured in vivo with a large dose of L-[4(-3)H]phenylalanine in 7- and 26-day-old pigs that were either fasted for 24 h or refed for 2.75 h after a 24-h fast. Fractional rates of protein synthesis (Ks) in skeletal muscle, heart, and liver were greater in 7-than in 26-day-old pigs. Refeeding stimulated Ks in skeletal muscle, pancreas, jejunum, and liver of both 7-and 26-day-old pigs. The stimulation of skeletal muscle and jejunal Ks by refeeding was greater in 7- than in 26-day-old pigs. Plasma IGF-I concentrations were lower in 7- than in 26-day-old pigs. Plasma concentrations of insulin and amino acids increased with refeeding. The increase in plasma insulin concentrations with refeeding was greater in 7- than in 26-days-old pigs. These results indicate that the stimulation in skeletal muscle and jejunal protein synthesis by feeding is elevated in young compared with older suckling pigs. This enhanced stimulation of protein synthesis by feeding in neonatal pigs is associated with elevated circulating concentrations of insulin but not amino acids or IGF-I.

scholarly journals Acute IGF-I infusion stimulates protein synthesis in skeletal muscle and other tissues of neonatal pigs

2002 ◽  
Vol 283 (4) ◽  
pp. E638-E647 ◽  
Author(s):  
Teresa A. Davis ◽  
Marta L. Fiorotto ◽  
Douglas G. Burrin ◽  
Rhonda C. Vann ◽  
Peter J. Reeds ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Cardiac Muscle ◽  
Liver Protein ◽  
Tissue Protein ◽  
Neonatal Pigs ◽  
Igf I ◽  
Tissue Protein Synthesis ◽  
Insulin Replacement

Studies have shown that protein synthesis in skeletal muscle of neonatal pigs is uniquely sensitive to a physiological rise in both insulin and amino acids. Protein synthesis in cardiac muscle, skin, and spleen is responsive to insulin but not amino acid stimulation, whereas in the liver, protein synthesis responds to amino acids but not insulin. To determine the response of protein synthesis to insulin-like growth factor I (IGF-I) in this model, overnight-fasted 7- and 26-day-old pigs were infused with IGF-I (0, 20, or 50 μg · kg−1 · h−1) to achieve levels within the physiological range, while amino acids and glucose were clamped at fasting levels. Because IGF-I infusion lowers circulating insulin levels, an additional group of high-dose IGF-I-infused pigs was also provided replacement insulin (10 ng · kg−0.66 · min−1). Tissue protein synthesis was measured using a flooding dose ofl-[4-3H]phenylalanine. In 7-day-old pigs, low-dose IGF-I increased protein synthesis by 25–60% in various skeletal muscles as well as in cardiac muscle (+38%), skin (+24%), and spleen (+32%). The higher dose of IGF-I elicited no further increase in protein synthesis above that found with the low IGF-I dose. Insulin replacement did not alter the response of protein synthesis to IGF-I in any tissue. The IGF-I-induced increases in tissue protein synthesis decreased with development. IGF-I infusion, with or without insulin replacement, had no effect on protein synthesis in liver, jejunum, pancreas, or kidney. Thus the magnitude, tissue specificity, and developmental change in the response of protein synthesis to acute physiological increases in plasma IGF-I are similar to those previously observed for insulin. This study provides in vivo data indicating that circulating IGF-I and insulin act on the same signaling components to stimulate protein synthesis and that this response is highly sensitive to stimulation in skeletal muscle of the neonate.

scholarly journals More than just a garbage can: emerging roles of the lysosome as an anabolic organelle in skeletal muscle

2020 ◽  
Vol 319 (3) ◽  
pp. C561-C568
Author(s):  
Sidney Abou Sawan ◽  
Michael Mazzulla ◽  
Daniel R. Moore ◽  
Nathan Hodson
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Intracellular Signaling ◽  
Muscle Protein ◽  
Future Research ◽  
Dietary Amino Acids ◽  
Lysosome Biogenesis ◽  
Transcription Factor Eb ◽  
Mtorc1 Activation

Skeletal muscle is a highly plastic tissue capable of remodeling in response to a range of physiological stimuli, including nutrients and exercise. Historically, the lysosome has been considered an essentially catabolic organelle contributing to autophagy, phagocytosis, and exo-/endocytosis in skeletal muscle. However, recent evidence has emerged of several anabolic roles for the lysosome, including the requirement for autophagy in skeletal muscle mass maintenance, the discovery of the lysosome as an intracellular signaling hub for mechanistic target of rapamycin complex 1 (mTORC1) activation, and the importance of transcription factor EB/lysosomal biogenesis-related signaling in the regulation of mTORC1-mediated protein synthesis. We, therefore, propose that the lysosome is an understudied organelle with the potential to underpin the skeletal muscle adaptive response to anabolic stimuli. Within this review, we describe the molecular regulation of lysosome biogenesis and detail the emerging anabolic roles of the lysosome in skeletal muscle with particular emphasis on how these roles may mediate adaptations to chronic resistance exercise. Furthermore, given the well-established role of amino acids to support muscle protein remodeling, we describe how dietary proteins “labeled” with stable isotopes could provide a complementary research tool to better understand how lysosomal biogenesis, autophagy regulation, and/or mTORC1-lysosomal repositioning can mediate the intracellular usage of dietary amino acids in response to anabolic stimuli. Finally, we provide avenues for future research with the aim of elucidating how the regulation of this important organelle could mediate skeletal muscle anabolism.

scholarly journals Amino acid-induced stimulation of translation initiation in rat skeletal muscle

1999 ◽  
Vol 277 (6) ◽  
pp. E1077-E1086 ◽  
Author(s):  
Thomas C. Vary ◽  
Leonard S. Jefferson ◽  
Scot R. Kimball
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Translation Initiation ◽  
Amino Acid Supplementation ◽  
Initiation Factors ◽  
Eukaryotic Initiation Factors ◽  
Amino Acid Concentrations ◽  
Stimulation Of

Amino acids stimulate protein synthesis in skeletal muscle by accelerating translation initiation. In the two studies described herein, we examined mechanisms by which amino acids regulate translation initiation in perfused skeletal muscle hindlimb preparation of rats. In the first study, the effects of supraphysiological amino acid concentrations on eukaryotic initiation factors (eIF) 2B and 4E were compared with physiological concentrations of amino acids. Amino acid supplementation stimulated protein synthesis twofold. No changes were observed in eIF2B activity, in the amount of eIF4E associated with the eIF4E-binding protein (4E-BP1), or in the phosphorylation of 4E-BP1. The abundance of eIF4E bound to eIF4G and the extent of phosphorylation of eIF4E were increased by 800 and 20%, respectively. In the second study, we examined the effect of removing leucine on translation initiation when all other amino acids were maintained at supraphysiological concentrations. Removal of leucine from the perfusate decreased the rate of protein synthesis by 40%. The inhibition of protein synthesis was associated with a 40% decrease in eIF2B activity and an 80% fall in the abundance of eIF4E ⋅ eIF4G complex. The fall in eIF4G binding to eIF4E was associated with increased 4E-BP1 bound to eIF4E and a reduced phosphorylation of 4E-BP1. In contrast, the extent of phosphorylation of eIF4E was unaffected. We conclude that formation of the active eIF4E ⋅ eIF4G complex controls protein synthesis in skeletal muscle when the amino acid concentration is above the physiological range, whereas removal of leucine reduces protein synthesis through changes in both eIF2B and eIF4E.

Stimulation of protein synthesis by both insulin and amino acids is unique to skeletal muscle in neonatal pigs

2002 ◽  
Vol 282 (4) ◽  
pp. E880-E890 ◽  
Author(s):  
Teresa A. Davis ◽  
Marta L. Fiorotto ◽  
Douglas G. Burrin ◽  
Peter J. Reeds ◽  
Hanh V. Nguyen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Skeletal Muscles ◽  
Insulin Infusion ◽  
Acid Mixture ◽  
Neonatal Pigs ◽  
Sarcoplasmic Proteins ◽  
Stimulation Of

In neonatal pigs, the feeding-induced stimulation of protein synthesis in skeletal muscle, but not liver, can be reproduced by insulin infusion when essential amino acids and glucose are maintained at fasting levels. In the present study, 7- and 26-day-old pigs were studied during 1) fasting, 2) hyperinsulinemic-euglycemic-euaminoacidemic clamps, 3) euinsulinemic-euglycemic-hyperaminoacidemic clamps, and 4) hyperinsulinemic-euglycemic-hyperaminoacidemic clamps. Amino acids were clamped using a new amino acid mixture enriched in nonessential amino acids. Tissue protein synthesis was measured using a flooding dose ofl-[4-3H]phenylalanine. In 7-day-old pigs, insulin infusion alone increased protein synthesis in various skeletal muscles (from +35 to +64%), with equivalent contribution of myofibrillar and sarcoplasmic proteins, as well as cardiac muscle (+50%), skin (+34%), and spleen (+26%). Amino acid infusion alone increased protein synthesis in skeletal muscles (from +28 to +50%), also with equivalent contribution of myofibrillar and sarcoplasmic proteins, as well as liver (+27%), pancreas (+28%), and kidney (+10%). An elevation of both insulin and amino acids did not have an additive effect. Similar qualitative results were obtained in 26-day-old pigs, but the magnitude of the stimulation of protein synthesis by insulin and/or amino acids was lower. The results suggest that, in the neonate, the stimulation of protein synthesis by feeding is mediated by either amino acids or insulin in most tissues; however, the feeding-induced stimulation of protein synthesis in skeletal muscle is uniquely regulated by both insulin and amino acids.

scholarly journals 146 Prematurity Blunts the Protein Synthetic Response of Skeletal Muscle to Insulin and Amino Acids

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 118-119
Author(s):  
Teresa A Davis ◽  
Marko Rudar ◽  
Jane Naberhuis ◽  
Agus Suryawan ◽  
Marta Fiorotto
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Body Weight Gain ◽  
Human Infant ◽  
Long Term Effects ◽  
Plasma Insulin Concentration ◽  
Akt Phosphorylation ◽  
Relative Body Weight

Abstract Livestock animals are important dual-purpose models that benefit both agricultural and biomedical research. The neonatal pig is an appropriate model for the human infant to assess long-term effects of early life nutrition on growth and metabolic outcomes. Previously we have demonstrated that prematurity blunts the feeding-induced stimulation of translation initiation and protein synthesis in skeletal muscle of neonatal pigs. The objective of this study was to determine whether reduced sensitivity to insulin and/or amino acids drives this blunted response. Pigs were delivered by caesarean section at preterm (PT, 103 d gestation) or at term (T, 112 d gestation) and fed parenterally for 4 d. On day 4, pigs were subject to euinsulinemic-euaminoacidemic-euglycemic (FAST), hyperinsulinemic-euaminoacidemic-euglycemic (INS), or euinsulinemic-hyperaminoacidemic-euglycemic (AA) clamps for 120 min, yielding six treatments: PT-FAST (n = 7), PT-INS (n = 9), PT-AA (n = 9), T-FAST (n = 8), T-INS (n = 9), and T-AA (n = 9). A flooding dose of L-[4-3H]Phe was injected into pigs 30 min before euthanasia. Birth weight and relative body weight gain were lower in PT than T pigs (P < 0.001). Plasma insulin concentration was increased from ~3 to ~100 µU/mL in INS compared to FAST and AA pigs (P < 0.001); plasma BCAA concentration was increased from ~250 to ~1,000 µmol/L in AA compared to FAST and INS pigs (P < 0.001). Despite achieving similar insulin and amino acid levels, longissimus dorsi AKT phosphorylation, mechanistic target of rapamycin (mTOR)·Rheb abundance, mTOR activation, and protein synthesis were lower in PT-INS than T-INS pigs (Table 1). Although amino-acid induced dissociation of Sestrin2 from GATOR2 was not affected by prematurity, mTOR·RagA abundance, mTOR·RagC abundance, mTOR activation, and protein synthesis were lower in PT-AA than T-AA pigs. The impaired capacity of premature skeletal muscle to respond to insulin or amino acids and promote protein synthesis likely contributes to reduced lean mass accretion. Research was supported by NIH and USDA.

scholarly journals Identification in skeletal muscle of a distinct extracellular pool of amino acids, and its role in protein synthesis

1971 ◽  
Vol 121 (5) ◽  
pp. 817-827 ◽  
Author(s):  
R. C. Hider ◽  
E. B. Fern ◽  
D. R. London
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Incubation Medium ◽  
Extensor Digitorum Longus ◽  
Extensor Digitorum ◽  
Longus Muscle ◽  
Kinetics Of

1. The kinetics of radioactive labelling of extra- and intra-cellular amino acid pools and protein of the extensor digitorum longus muscle were studied after incubations with radioactive amino acids in vitro. 2. The results indicated that an extracellular pool could be defined, the contents of which were different from those of the incubation medium. 3. It was concluded that amino acids from the extracellular pool, as defined in this study, were incorporated directly into protein.

Growth hormone acutely stimulates forearm muscle protein synthesis in normal humans

1991 ◽  
Vol 260 (3) ◽  
pp. E499-E504 ◽  
Author(s):  
D. A. Fryburg ◽  
R. A. Gelfand ◽  
E. J. Barrett
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Growth Hormone ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Skeletal Muscle Protein ◽  
Skeletal Muscle Protein Synthesis ◽  
Igf I ◽  
Normal Humans

The short-term effects of growth hormone (GH) on skeletal muscle protein synthesis and degradation in normal humans are unknown. We studied seven postabsorptive healthy men (age 18-23 yr) who received GH (0.014 micrograms.kg-1.min-1) via intrabrachial artery infusion for 6 h. The effects of GH on forearm amino acid and glucose balances and on forearm amino acid kinetics [( 3H]Phe and [14C]Leu) were determined after 3 and 6 h of the GH infusion. Forearm deep vein GH rose to 35 +/- 6 ng/ml in response to GH, whereas systemic levels of GH, insulin, and insulin-like growth factor I (IGF-I) were unchanged. Forearm glucose uptake did not change during the study. After 6 h, GH suppressed forearm net release (3 vs. 6 h) of Phe (P less than 0.05), Leu (P less than 0.01), total branched-chain amino acids (P less than 0.025), and essential neutral amino acids (0.05 less than P less than 0.1). The effect on the net balance of Phe and Leu was due to an increase in the tissue uptake for Phe (71%, P less than 0.05) and Leu (37%, P less than 0.005) in the absence of any significant change in release of Phe or Leu from tissue. In the absence of any change in systemic GH, IGF-I, or insulin, these findings suggest that locally infused GH stimulates skeletal muscle protein synthesis. These findings have important physiological implications for both the role of daily GH pulses and the mechanisms through which GH can promote protein anabolism.

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