scholarly journals Effects of Growth Hormone on Leptin Metabolism and Energy Expenditure in Hemodialysis Patients with Protein-Calorie Malnutrition

2000 ◽  
Vol 11 (11) ◽  
pp. 2106-2113
Author(s):  
GIACOMO GARIBOTTO ◽  
ANTONINA BARRECA ◽  
ANTONELLA SOFIA ◽  
RODOLFO RUSSO ◽  
FULVIO FIORINI ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Protein Synthesis ◽  
Energy Expenditure ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Resting Energy Expenditure ◽  
Hemodialysis Patients ◽  
Gh Treatment ◽  
Peripheral Tissues

Abstract. The relationships among growth hormone (GH), leptin, and resting energy expenditure (REE) are not understood. It has been reported that in malnourished hemodialysis patients, GH increases muscle protein synthesis, a process that requires energy. The present study evaluated the arterial levels and the forearm exchange of leptin, as well as the REE of the same patients during their participation in the same study, in four sequential 6-wk periods: I, baseline; II, GH treatment; III, washout; and IV, GH + intradialytic parenteral nutrition. During periods II and IV, patients received GH (5 mg three times per week). REE rose by 5% in period II, declined during period III, and rose by 7% during period IV. Basal leptin levels were low (2.0 ± 0.19 ng/L). Insulin and leptin levels, as well as leptin release from the forearm, were unchanged during periods I through III but rose (+ 36%; P < 0.05) during period IV. Changes in arterial leptin were directly related to changes in forearm leptin release (P < 0.002), indicating a role of leptin production by peripheral tissues on leptinemia. Changes in leptin release were directly related to insulin (P < 0.001) and, less consistently, to insulin-like growth factor-binding protein-1 levels (P < 0.02). Similarly, variations in leptin levels were directly related to insulin (P < 0.01). Variations in REE were not related to variations in leptin or insulin levels but to changes in muscle protein synthesis (P < 0.025). The data show that in malnourished hemodialysis patients, treatment with GH is not invariably associated with an increase in leptin production. An increase in leptin release by peripheral tissues and leptin levels occurs only in the setting of hyperinsulinemia. The increase in REE that is induced by treatment with GH is not dependent on changes in leptin but is largely accounted for by the energy cost of the stimulation of muscle protein synthesis.

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.

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.

scholarly journals Advances in the Role of Leucine-Sensing in the Regulation of Protein Synthesis in Aging Skeletal Muscle

2021 ◽  
Vol 9 ◽  
Author(s):  
Yan Zhao ◽  
Jason Cholewa ◽  
Huayu Shang ◽  
Yueqin Yang ◽  
Xiaomin Ding ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Therapeutic Potential ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Trna Synthetase ◽  
Limiting Factor ◽  
Anabolic Resistance ◽  
Age Related

Skeletal muscle anabolic resistance (i.e., the decrease in muscle protein synthesis (MPS) in response to anabolic stimuli such as amino acids and exercise) has been identified as a major cause of age-related sarcopenia, to which blunted nutrition-sensing contributes. In recent years, it has been suggested that a leucine sensor may function as a rate-limiting factor in skeletal MPS via small-molecule GTPase. Leucine-sensing and response may therefore have important therapeutic potential in the steady regulation of protein metabolism in aging skeletal muscle. This paper systematically summarizes the three critical processes involved in the leucine-sensing and response process: (1) How the coincidence detector mammalian target of rapamycin complex 1 localizes on the surface of lysosome and how its crucial upstream regulators Rheb and RagB/RagD interact to modulate the leucine response; (2) how complexes such as Ragulator, GATOR, FLCN, and TSC control the nucleotide loading state of Rheb and RagB/RagD to modulate their functional activity; and (3) how the identified leucine sensor leucyl-tRNA synthetase (LARS) and stress response protein 2 (Sestrin2) participate in the leucine-sensing process and the activation of RagB/RagD. Finally, we discuss the potential mechanistic role of exercise and its interactions with leucine-sensing and anabolic responses.

scholarly journals Citrulline directly modulates muscle protein synthesis via the PI3K/MAPK/4E-BP1 pathway in a malnourished state: evidence from in vivo, ex vivo, and in vitro studies

2017 ◽  
Vol 312 (1) ◽  
pp. E27-E36 ◽  
Author(s):  
Servane Le Plénier ◽  
Arthur Goron ◽  
Athanassia Sotiropoulos ◽  
Eliane Archambault ◽  
Chantal Guihenneuc ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Ex Vivo ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Fold Increase ◽  
Underlying Mechanism ◽  
Muscle Homeostasis

Citrulline (CIT) is an endogenous amino acid produced by the intestine. Recent literature has consistently shown CIT to be an activator of muscle protein synthesis (MPS). However, the underlying mechanism is still unknown. Our working hypothesis was that CIT might regulate muscle homeostasis directly through the mTORC1/PI3K/MAPK pathways. Because CIT undergoes both interorgan and intraorgan trafficking and metabolism, we combined three approaches: in vivo, ex vivo, and in vitro. Using a model of malnourished aged rats, CIT supplementation activated the phosphorylation of S6K1 and 4E-BP1 in muscle. Interestingly, the increase in S6K1 phosphorylation was positively correlated ( P < 0.05) with plasma CIT concentration. In a model of isolated incubated skeletal muscle from malnourished rats, CIT enhanced MPS (from 30 to 80% CIT vs. Ctrl, P < 0.05), and the CIT effect was abolished in the presence of wortmannin, rapamycin, and PD-98059. In vitro, on myotubes in culture, CIT led to a 2.5-fold increase in S6K1 phosphorylation and a 1.5-fold increase in 4E-BP1 phosphorylation. Both rapamycin and PD-98059 inhibited the CIT effect on S6K1, whereas only LY-294002 inhibited the CIT effect on both S6K1 and 4E-BP1. These findings show that CIT is a signaling agent for muscle homeostasis, suggesting a new role of the intestine in muscle mass control.

Glucose flux is normalized by compensatory hyperinsulinaemia in growth hormone-induced insulin resistance in healthy subjects, while skeletal muscle protein synthesis remains unchanged

2002 ◽  
Vol 102 (4) ◽  
pp. 457-464 ◽  
Author(s):  
Jonas NYGREN ◽  
Anders THORELL ◽  
Kerstin BRISMAR ◽  
Pia ESSÉN ◽  
Jan WERNERMAN ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Glucose Infusion ◽  
Skeletal Muscle Protein ◽  
Gh Treatment ◽  
Glucose Flux ◽  
Skeletal Muscle Protein Synthesis ◽  
Igf Binding

The aim of this present investigation was to study the relationship between the reduction in insulin sensitivity accompanying 5 days of treatment with growth hormone (GH; 0.05mgċ24h-1ċkg-1) and intracellular substrate oxidation rates in six healthy subjects, while maintaining glucose flux by a constant glucose infusion and adjusting insulin infusion rates to achieve normoglycaemia (feedback clamp). Protein synthesis rates in skeletal muscle (flooding dose of L-[2H5]phenylalanine) were determined under these conditions. We also compared changes in insulin sensitivity after GH treatment with simultaneous changes in energy requirements, protein synthesis rates, nitrogen balance, 3-methylhistidine excretion in urine, body composition and the hormonal milieu. After GH treatment, 70% more insulin was required to maintain normoglycaemia (P < 0.01). The ratio between glucose infusion rate and serum insulin levels decreased by 34% at the two levels of glucose infusion tested (P < 0.05). Basal levels of C-peptide, insulin-like growth factor (IGF)-I and IGF-binding protein-3 increased almost 2-fold, while levels of glucose, insulin, glucagon, GH and IGF-binding protein-1 remained unchanged. Non-esterified fatty acid levels decreased (P < 0.05). In addition, 24h urinary nitrogen excretion decreased by 26% (P < 0.01) after GH treatment, while skeletal muscle protein synthesis and 3-methylhistidine excretion in urine remained unchanged. Energy expenditure increased by 5% (P < 0.05) after treatment, whereas fat and carbohydrate oxidation were unaltered. In conclusion, when glucose flux was normalized by compensatory hyperinsulinaemia under conditions of GH-induced insulin resistance, intracellular rates of oxidation of glucose and fat remained unchanged. The nitrogen retention accompanying GH treatment seems to be due largely to improved nitrogen balance in non-muscle tissue.

Effects of growth hormone and an antiserum to rat growth hormone on serum IGF-I and muscle protein synthesis and accretion in the rat

1993 ◽  
Vol 139 (3) ◽  
pp. 395-401 ◽  
Author(s):  
R. M. Palmer ◽  
D. J. Flint ◽  
J. C. MacRae ◽  
F. E. Fairhurst ◽  
L. A. Bruce ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Protein Synthesis ◽  
Protein Content ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Polyclonal Antiserum ◽  
Whole Body ◽  
Total Protein Content ◽  
Plantaris Muscle ◽  
Igf I

ABSTRACT Rats were injected twice daily for up to 10 days with GH or with a polyclonal antiserum to rat GH, commencing at 21–22 days of age. Administration of bovine or human GH (1 mg/day) improved whole body growth rates by 22% and 29% respectively. Plantaris muscle mass was also increased, by 7 and 14% respectively. Anti-GH injected twice daily resulted in a 7% decrease in body weight at 4 days and a 10% reduction by 10 days. Similar decreases were observed in the total protein content of plantaris and soleus muscles. The decrease in the fractional rate of protein synthesis was proportionately greater than the decline in protein content in plantaris muscle whereas in the soleus no change in the rate of protein synthesis was observed, suggesting that the effect on this muscle was due to an increase in the rate of protein degradation. Serum total IGF-I was unchanged by treatment with either GH or anti-GH while the amount of hepatic IGF-I mRNA was also unaffected by anti-GH injection. These data are consistent with a direct effect of GH or an effect mediated by an autocrine/paracrine mechanism of action on muscle but do not support a role for serum total IGF-I as an endocrine mediator of GH action. Journal of Endocrinology (1993) 139, 395–401

Beyond muscle hypertrophy: why dietary protein is important for endurance athletes

2014 ◽  
Vol 39 (9) ◽  
pp. 987-997 ◽  
Author(s):  
Daniel R. Moore ◽  
Donny M. Camera ◽  
Jose L. Areta ◽  
John A. Hawley
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Dietary Protein ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Recovery Period ◽  
Essential Element ◽  
Skeletal Muscle Protein ◽  
Muscle Remodelling

Recovery from the demands of daily training is an essential element of a scientifically based periodized program whose twin goals are to maximize training adaptation and enhance performance. Prolonged endurance training sessions induce substantial metabolic perturbations in skeletal muscle, including the depletion of endogenous fuels and damage/disruption to muscle and body proteins. Therefore, increasing nutrient availability (i.e., carbohydrate and protein) in the post-training recovery period is important to replenish substrate stores and facilitate repair and remodelling of skeletal muscle. It is well accepted that protein ingestion following resistance-based exercise increases rates of skeletal muscle protein synthesis and potentiates gains in muscle mass and strength. To date, however, little attention has focused on the ability of dietary protein to enhance skeletal muscle remodelling and stimulate adaptations that promote an endurance phenotype. The purpose of this review is to critically discuss the results of recent studies that have examined the role of dietary protein for the endurance athlete. Our primary aim is to consider the results from contemporary investigations that have advanced our knowledge of how the manipulation of dietary protein (i.e., amount, type, and timing of ingestion) can facilitate muscle remodelling by promoting muscle protein synthesis. We focus on the role of protein in facilitating optimal recovery from, and promoting adaptations to strenuous endurance-based training.

Control of Muscle Protein Synthesis as a Result of Contractile Activity and Amino Acid Availability: Implications for Protein Requirements

2001 ◽  
Vol 11 (s1) ◽  
pp. S170-S176 ◽  
Author(s):  
Michael J. Rennie
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Contractile Activity ◽  
Muscle Protein Synthesis ◽  
Protein Requirements ◽  
Amino Acid Availability ◽  
Separate Pathway

The major anabolic influences on muscle are feeding and contractile activity. As a result of feeding, anabolism occurs chiefly by increases in protein synthesis with minor changes in protein breakdown. Insulin has a permissive role in increasing synthesis, but the availability of amino acids is crucial for net anabolism. We have investigated the role of amino acids in stimulating muscle protein synthesis, the synergy between exercise and amino acid availability, and some of the signaling elements involved. The results suggest that muscle is acutely sensitive to amino acids, that exercise probably increases the anabolic effects of amino acids by a separate pathway, and that for this reason it is unlikely that accustomed physical exercise increases protein requirements.

scholarly journals Increased energy expenditure in hemodialysis patients.

1996 ◽  
Vol 7 (12) ◽  
pp. 2646-2653
Author(s):  
T A Ikizler ◽  
R L Wingard ◽  
M Sun ◽  
J Harvell ◽  
R A Parker ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Respiratory Quotient ◽  
Resting Energy Expenditure ◽  
Hemodialysis Patients ◽  
Chronic Hemodialysis ◽  
Multiple Factors ◽  
Control Subjects ◽  
Protein Calorie Malnutrition ◽  
Resting Energy

Malnutrition is prevalent in chronic hemodialysis patients and is related to multiple factors; the hemodialysis procedure itself has been suggested as a catabolic factor. To examine the possible role of hemodialysis on energy metabolism, resting energy expenditure and respiratory quotient in ten chronic hemodialysis patients was measured in this study, using a whole-room indirect calorimeter. Measurements were done continuously: for 2 h before hemodialysis, during 4 h of hemodialysis, for 2 h after hemodialysis, and separately on a nondialysis day after 12 h of fasting. Age-, sex-, and body mass index-matched healthy volunteers were used as control subjects. Chronic hemodialysis patients have a significantly higher resting energy expenditure on a nondialysis day (1.18 +/- 0.15 kcal/min; P < 0.01) as compared with control subjects (1.10 +/- 0.16 kcal/ min). Resting energy expenditure further increased significantly during the hemodialysis procedure (1.32 +/- 0.18 kcal/min, averaged over the 4 h of hemodialysis; P < 0.01 versus predialysis) and was also significantly higher compared with the postdialysis period and nondialysis day resting energy expenditure (P < 0.001 for both). This effect was most pronounced during the first (1.37 +/- 0.19 kcal/min) and second (1.33 +/- 0.18 kcal/min) hours of hemodialysis (P < 0.001 for both). Respiratory quotient was not significantly affected by hemodialysis. It was concluded that chronic hemodialysis patients have higher than normal resting energy expenditure levels, which is further increased during hemodialysis. This process may significantly potentiate the protein-calorie malnutrition seen in this patient population.

scholarly journals Exercise-Induced Muscle Damage and Hypertrophy: A Closer Look Reveals the Jury is Still Out

2018 ◽  
Author(s):  
Brad Jon Schoenfeld ◽  
Bret Contreras
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Resistance Training ◽  
Muscle Damage ◽  
Muscle Hypertrophy ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Skeletal Muscle Hypertrophy ◽  
Exercise Induced

This letter is a response to the paper by Damas et al (2017) titled, “The development of skeletal muscle hypertrophy through resistance training: the role of muscle damage and muscle protein synthesis,” which, in part, endeavored to review the role of exercise-induced muscle damage on muscle hypertrophy. We feel there are a number of issues in interpretation of research and extrapolation that preclude drawing the inference expressed in the paper that muscle damage neither explains nor potentiates increases in muscle hypertrophy. The intent of our letter is not to suggest that a causal role exists between hypertrophy and microinjury. Rather, we hope to provide balance to the evidence presented and offer the opinion that the jury is still very much out as to providing answers on the topic.

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