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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deprivation of food caused significant changes in the weight, protein content, protein turnover and RNA concentrations of the extensor digitorum longus muscle. Simultaneous immobilization to render the muscle inactive did not make the tissue any more susceptible to the effects of starvation. In contrast, immobilization in a stretched state resulted in less muscle wasting after deprivation of food.
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PMID:The effects of food deprivation on protein turnover and nucleic acid concentrations of active and immobilized extensor digitorum longus muscles of the rat. 74 62

This article reviews work we have carried out to investigate (1) the transport mechanisms responsible for the high distribution ratio of free glutamine commonly observed in skeletal muscle; (2) the fall in the distribution ratio that accompanies starvation, injury and chronic disease, whether directly involving muscle or not; and (3) the effect of modulation of intracellular free-glutamine concentration on protein synthesis and breakdown in skeletal muscle. We suggest that the results are consistent with the controlling role of the muscle membrane glutamine-sodium cotransporter in the regulation of the intracellular glutamine pool, the existence of pathophysiological mechanisms for the modulation of intramuscular glutamine and anabolic effects of glutamine in promoting protein synthesis, with a smaller effect in reducing protein breakdown. The mechanisms by which glutamine affects skeletal muscle protein turnover, and thus muscle protein balance, and the extent of the net flow of amino acids between the periphery and the viscera are unknown as yet, but the results suggest that modulation of transporter activity may offer the possibility of therapeutic intervention to reduce muscle wasting associated with injury and disease.
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PMID:Skeletal muscle glutamine transport, intramuscular glutamine concentration, and muscle-protein turnover. 266 3

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.
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PMID:The effect of glucagon administration on protein synthesis in skeletal muscles, heart and liver in vivo. 389 31

The marine telost Pollachius virens undergoes a natural starvation during the winter, and provides a reversible, non-pathological model for studying muscle wasting. In the present study fish were kept without food under laboratory conditions for up to 12 weeks. The effects of starvation on muscle fibre size, volume fractions of mitochondria and myofibrils, and capillary supply were determined. Starvation results in a preferential atrophy and degradation of fast muscle myofibrillar proteins. For example, fibre cross-sectional area decreased from 1014 to 535 micrometers 2 (p less than 0.005) and myofibrillar volume fraction from 79.0% to 56.4% (p less than 0.001) in fast fibres following 12 weeks starvation. In contrast there was little change in these parameters in slow muscle fibres. Evidence is presented that M-line and Z-disc breakdown occur as an initial stage of myofibrillar degradation. Sarcoplasmic reticulum in atrophied fibres often appeared swollen and multi-membraned lysosome-like vesicles were common. The percentage of slow fibres (44 to 64%; p less than 0.025) and fast fibers (51 to 86%; p less than 0.01) without capillary contact increased and the percentage of fibre perimeter vascularised decreased during a 12 week starvation (6.3 to 3.3% in slow fibres and 2.8 to 1.1% fast fibres). The volume fractions of mitochondria in slow fibres decreased in parallel to the decrease in capillary supply (from 34.6 to 18.6%; p less than 0.001). Mechanisms of myofibrillar degradation during muscle wasting are discussed.
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PMID:Muscle atrophy during starvation in a marine teleost. 683 67

The present study describes the effects of starvation for a duration of four months on the ultrastructure of skeletal muscles from the marine flatfish (Pleuronectes platessa L.). Starvation is associated with a decrease in resting metabolic rate from 20.1 +/- 2.2 to 11.6 +/- 1.5 mg . O2/kg/h (P less than 0.05) and muscle wasting. Median fibre size fell from 700 micrometer 2 to 500 micrometer 2 in intermediate (fast oxidative) and from 1,800 micrometer 2 to 600 micrometer 2 in starved, white (fast-glycolytic) muscle fibres. In contrast, median fibre size in red (slow oxidative) muscle remained within the range 300-400 micrometer 2. The fraction of red fibre volume occupied by myofibrils (58.6%) and mitochondria (24.5%) did not change significantly with starvation. There was, however, a decrease in stored lipid 110.7% to 3.2%) and an alteration in the structure of the cristae in mitochondria from red muscle. Atrophy of white muscle fibres is associated with a decrease in both the diameter and fractional volume occupied by myofibrils (85.7% to 61.9% P less than 0.01). In a high proportion of white fibres peripheral degeneration of Z-discs is evident causing an unravelling of the thin filament lattice. It is suggested that this allows a partial decrease in myofibril diameter and hence the maintenance of contractile function in muscle from starved fish. In severely degenerating white fibres, disorganised thick and thin filaments and numerous multi-membrane lysosome-like vesicles are observed. Starvation results in an increase in the average content of mitochondria in white fibres from 2.2 to 6.7% (P less than 0.01). In fed plaice mitochondria constitute less than 1% of the volume of the white fibre in 43.5% of the fibres. The proportion of white fibres containing more than 6% mitochondria increases from 6.5% to 58% with starvation.
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PMID:Quantitative analysis of muscle breakdown during starvation in the marine flatfish Pleuronectes platessa. 747 Nov 84

Impaired protein synthesis (PS) occurs in skeletal muscle during acute starvation. Even though it is well established that uraemic metabolic acidosis (MA) stimulates protein degradation (PD) and is a major contributor to skeletal muscle wasting in chronic renal failure, the accompanying effects of MA on PS are much less clear. Previous work has shown that, in cultured L6 skeletal muscle cells, PD and leucine oxidation are stimulated by acid. The aim of the present study was to determine whether acid (like acute starvation) can also inhibit PS. PS (14C-phenylalanine incorporation) was measured in L6 cells in MEM + 2% serum at acid pH (7.1) or control pH (7.5). After 24 h, acid inhibited PS (7.7 +/- 0.2 vs. 8.9 +/- 0.1 nmol Phe/4 h/35-mm culture well in controls, p = 0.01) and this was maintained at 72 h. In vitro this could arise because acid only inhibits the rapid PS occurring in dividing cells. However, when division was abolished with 10(-5) mol/l cytosine arabinoside, PS inhibition by acid still occurred (6.9 +/- 0.1 vs. 8.3 +/- 0.2 at control pH, p < 0.05). Acid also had no effect on the specific radioactivity of cellular phenylalanine, suggesting that the impaired PS was not a consequence of inadequate labelling of this pool. Elevated PD and impaired PS together led to loss of 7% of the total protein in only 28 h (-21 +/- 3 microg/well, p = 0.004). This combination of impaired PS with increased PD and increased leucine oxidation in response to acid resembles the response of skeletal muscle to acute starvation. These superficial similarities between the starvation state and MA suggest that fundamental metabolic signals may occur which are common to both states.
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PMID:Inhibition of protein synthesis by acid in L6 skeletal muscle cells: analogies with the acute starvation response. 955 65

Human subjects vary in the extent to which their body's protein and fat compartments are mobilized for fuel during starvation. Although an inverse association between the initial adiposity and the contribution of protein as fuel during starvation has been known for nearly a century, interest in the quantitative importance and functional significance of the initial percentage fat as a determinant of biological variation in energy-partitioning between protein and fat (and hence in determining the partitioning characteristic of the individual) is relatively recent. The present paper addresses these issues by revisiting the classic Minnesota experiment of semi-starvation and refeeding from a standpoint of system physiology. In a quantitative analysis of the relationship between the initial body composition (ration FAT0: fat-free mass (FFM)0) and the composition of weight loss (ratio delta FAT: delta FFM) in the thirty-two men in the Minnesota study, the arguments are put forward that the fraction of FFM lost when the fat stores reach total depletion is independent of the initial percentage fat, and that this fraction represents the 'dispensable' component of the protein compartment that is compatible with life (i.e. the protein energy-reserve, rp). The concepts are developed that (1) the initial percentage body fat (which reflects the initial ratio FAT0:FFM0) provides a 'memory of partitioning' which dictates the control of partitioning between protein and fat in such a way that both the protein energy-reserve (rp) and the fat energy-reserve (rf) each complete depletion simultaneously, a strategy that would ensure maximum length of survival during long-term food scarcity, and that (2) variability in the relative sizes of these two energy reserves (i.e. in rf:rp) could, in addition to the initial percentage fat, also contribute to human variability in energy-partitioning. The basic assumptions underlying this re-analysis of the Minnesota data, and the concepts that are derived from it, have been integrated in the simple mathematical model for predicting the partitioning characteristic of the individual. This model is used to explain how variability in the fraction of the protein compartment that could function as an energy reserve (rp) can be as important as the initial percentage fat in determining inter-individual variability in protein-sparing during the early phase of starvation, in fuel partitioning during prolonged starvation, or in the maximum percentage weight loss during starvation. The elucidation of factors underlying variability in the size of the protein energy-reserve may have important implications for our understanding of the pathophysiology of starvation and age-associated susceptibility to muscle wasting, and in the clinical management of cachexia and obesity.
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PMID:The control of partitioning between protein and fat during human starvation: its internal determinants and biological significance. 1067 6

Loss of muscle mass usually characterizes different pathologies (sepsis, cancer, trauma) and also occurs during normal aging. One reason for muscle wasting relates to a decrease in food intake. This study addressed the role of leucine as a regulator of protein breakdown in mouse C2C12 myotubes and aimed to determine which cellular responses regulate the process. Determination of the rate of protein breakdown indicated that leucine is one key regulator of this process in myotubes because starvation for this amino acid is responsible for 30-40% of the total increase generated by total amino acid starvation. Leucine restriction rapidly accelerates the rate of protein breakdown (+11 to 15% (p < 0.001) after 1 h of starvation) in a dose-dependent manner. By using various inhibitors, evidence is provided that acceleration of protein catabolism results mainly from an induction of autophagy, activation of lysosome-dependent proteolysis, without modification of mRNA levels encoding the lysosomal cathepsins B, L, or D. Those results suggest that autophagy is an essential cellular response for increasing protein breakdown in muscle following food deprivation. Induction of autophagy precedes a decrease in global protein synthesis (-20% to -30% (p < 0.001)) that occurs after 3 h of leucine starvation. Inhibition of the mammalian target of rapamycin (mTOR) activity does not abolish the effect of leucine starvation and the level of phosphorylated ribosomal S6 protein is not affected by leucine withdrawal. These latter data provide clear evidence that the mTOR signaling pathway is not involved in the mediation of leucine effects on both protein synthesis and degradation in C2C12 myotubes.
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PMID:Leucine limitation induces autophagy and activation of lysosome-dependent proteolysis in C2C12 myotubes through a mammalian target of rapamycin-independent signaling pathway. 1089 13

Combined effects of heavy-metal contamination (Cu, Zn, and CH3Hg) and starvation were tested on common quails (Coturnix coturnix japonica) and used as a model for comparison with a wild common guillemot (Uria aalge) population found stranded at the Belgian coast. Appropriate heavy-metal levels were given to the quails to obtain concentrations similar to those found in the seabirds's tissues. The contaminated animals were then starved for 4 d to simulate the evident malnutrition symptoms observed at the guillemot's level. In such conditions, food intake and total-body weight are shown to decrease in contaminated individuals with simultaneous significant hepatic and renal increase of the heavy-metal concentrations. Like guillemots, higher heavy-metal levels were observed in those contam- inated quails that had also developed a cachectic status characterized by a general atrophy of their pectoral muscle and complete absence of subcutaneous and/or abdominal fat depots. Although likely the result of a general protein catabolism during starvation, it is suggested that these higher metal levels could as well enhance a general muscle wasting process (cachectic status).
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PMID:Combined effects of experimental heavy-metal contamination (Cu, Zn, and CH3Hg) and starvation on quail's body condition: parallelism with a wild common guillemot (Uria aalge) population found stranded at the Belgian coast. 1169 81

The plasma concentration of an amino acid (AA) is the result of its rates of appearance (Ra) in and disappearance (Rd) from plasma. As for most nutrients, AA Ra and Rd are tightly regulated and at the postabsorptive state Ra equals Rd. Factors controlling Ra are protein intake and tissue release; those controlling Rd are tissue uptake and body losses (urine, sweat, etc.). Regulation of plasma AA concentrations involves hormones, in particular insulin and glucagon, both of which induce hypoaminoacidemia (but for quite different reasons), and cortisol, which induces hyperaminoacidemia. In addition, in pathologic states, catecholamines, thyroid hormones, and cytokines modulate plasma AA levels. Peripheral availability of AAs after protein ingestion is controlled by the liver, with an activation of ureagenesis in hyperprotein feeding and repression during a hypoprotein diet. The arginine-to-citrulline pathway in the intestine plays a key role in this adaptative process. In some circumstances tissue uptake of AAs and further metabolism depend on plasma AA concentrations. Plasma glutamine level may be the driving force controlling the flux of this AA at the muscle level. Also, channeling of the arginine cellular pathways means that plasma arginine is a major controlling component of nitric oxide synthesis in endothelial and immune cells. All these features explain the excessive increase in glutamine and arginine demands, in particular for energy expenditure, leading to morbidity (e.g., gut atrophy, muscle wasting, and immune dysfunction) in stressed patients. Normoaminoacidemia is not synonymous with health because this state is observed in level 2 starvation (Ra and Rd decrease) or after minor injury (Ra and Rd increase). Hyperaminoacidemia may be the consequence of organ failure (Rd decreases) or excessive AA intake during parenteral nutrition (Ra increases). Hypoaminoacidemia is observed after organ removal (Ra decreases, e.g., decrease in citrulline concentration in short bowel syndrome) or in stress situations (Rd increases). Mere determinations of plasma AA concentrations at the basal state (i.e., postabsorptive) provide rather limited information. Their usefulness can be improved by measuring arteriovenous differences or performing time course measurements, but techniques based on stable isotopes are necessary to obtain more precise information on the behavior of a particular AA or group of AAs.
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PMID:Plasma amino acid levels with a note on membrane transport: characteristics, regulation, and metabolic significance. 1229 20


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