Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study has evaluated the effects of recombinant human insulin-like growth factor I (rhIGF-I) to moderately stressed post-operative patients provided with dextrose as the only exogeneous substrate. Thirty patients who underwent elective colorectal surgery were randomized to receive either rhIGF-I (80 micrograms kg-1 bw) subcutaneously twice daily or placebo injections in a double-blind parallel group design. Nitrogen balance, urinary 3-methyl-histidine excretion plasma growth hormone (GH), serum cortisol, IGF-I binding proteins (IGFBP-1,3), glomerular filtration rate, plasma amino acid concentrations and whole-body energy expenditures were measured as effector variables during days 1-5 post-operatively. Animal and isolated tissue experiments were performed as additional control experiments to confirm cellular effectiveness of the recombinant material. rhIGF-I increased significantly the glomerular filtration rate and prevented the adaptive decrease in whole-body energy expenditure in response to partial starvation in the postoperative period. Serum and plasma concentrations of IGFBP-1,3 cortisol, blood glucose and amino acids were not significantly influenced by rhIGF-I administration, while plasma GH levels decreased significantly as expected. rhIGF-I had no effect on either nitrogen balance or protein breakdown (3-methylhistidine excretion) in post-operative patients on dextrose supplementation only, although plasma concentrations of IGF-I increased from 130-140 ng mL-1 to a range of 300-450 ng mL-1. In contrast, IGF-I stimulated the synthesis of both globular and myofibrillar proteins (+50%, P < 0.01), when given as a single dose (100 micrograms kg-1) 2 h before measurements of protein synthesis in skeletal muscles of overnight fasted adult mice. This stimulatory effect by IGF-I (1 microgram mL-1) was also confirmed by measurements of skeletal muscle protein synthesis in vitro (+40%, P < 0.05). Orally re-fed mice had a normal transcription of IGF-I mRNA in skeletal muscle cells, while overnight fasted mice showed a trend to down-regulated transcription. Our results demonstrate that rhIGF-I has several significant physiological effects, without major side-effects, when supplied to partially starved patients in the post-operative phase. The lack of a whole-body nitrogen sparing effect by rhIGF-I alone to post-operative patients is not clear, but was most likely explained by subnormal plasma concentrations of amino acids.
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PMID:The effect of recombinant human IGF-I on protein metabolism in post-operative patients without nutrition compared to effects in experimental animals. 855 66

The adaptation to fasting reduces muscle protein breakdown by switching from a carbohydrate to fat fuel economy in normal man. With the discovery of T3 and the observation that its formation from T4 was reduced significantly during starvation, it was proposed that T3 mediated many of these changes. To examine this possibility, otherwise healthy, obese subjects were fasted for 10 days and supplemented with T3 the last 3 days of the fast to bring circulating T3 levels within normal prefasting (weight maintenance) levels. The effects of the same dose of T3 for 3 days were tested during the last 3 days of a 10-day weight maintenance diet for comparison. Both metabolic rate and CO2 production decreased as expected with fasting and did not increase after T3 supplementation. Hepatic glucose appearance rates fell with fasting and increased significantly during T4 supplementation, but not to prefasting levels. Urinary urea nitrogen excretion decreased significantly with fasting and decreased further with T3 supplementation. Lysine appearance did not change during fasting or T3 supplementation, but leucine appearance decreased with T3 supplementation during fasting. These observations suggest that the fall in serum T3 during fasting may not mediate the observed decreases in protein breakdown that occur during fasting and prolonged starvation, but may instead initiate the fall in hepatic glucose appearance.
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PMID:Metabolic effects of triiodothyronine replacement during fasting in obese subjects. 877 59

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.
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PMID:Role of insulin and IGF-I in activation of muscle protein synthesis after oral feeding. 892 67

Rats were fasted for 48 h, but infused with either NaCl or the sodium salt of monoethyl succinic acid (EMS), both delivered at a rate of 80 mumol/g body weight per day. The infusion of EMS, as compared to NaCl, failed to affect paraovarian adipose tissue or liver weight, liver or muscle glycogen, and insulinemia. It accentuated the starvation-induced fall in body weight, and decreased both liver and muscle protein content. Nevertheless, the succinate ester increased plasma D-glucose concentration, delayed the rise in ketonemia, maintained a higher glucokinase/hexokinase activity ratio in liver and pancreatic islets, and allowed for a more efficient stimulation of insulin release by D-glucose or 2-ketoisocaproate in isolated pancreatic islets. These findings indicate that monoethyl succinate displays a significant nutritional value when infused in starved rats.
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PMID:Nutritional value of succinic acid monoethyl ester in starvation. 926 86

Rainbow smelt, Osmerus mordax, maintain high glycerol levels in winter to avoid freezing. After intramuscular injection of 14C-labeled glucose, [14C]glycerol was found in the blood, liver and muscle, indicating that glycogen is a source of glycerol. Levels of both the active and inactive forms of glycogen phosphorylase were higher in muscle in winter than in autumn, although the fraction in the active form did not change significantly. More of the phosphorylase was in the active form in the liver than in the muscle. Short-term starvation resulted in a significant decrease in the level of glycogen soon after the stomachs were emptied, presumably to replace glycerol lost to the water. However, tissue glycerol levels remained relatively high, despite a near depletion of glycogen reserves. Triglyceride levels increased slightly during starvation, indicating that triglycerides were not involved in glycerol synthesis. After intramuscular injection of 14C-labeled pyruvate, [14C]glycerol was found in the blood, liver and muscle, indicating a second route, presumably from muscle protein, to glycerol synthesis. Liver phosphoenolpyruvate carboxykinase activity was slightly higher in winter, possibly to assist in the conversion of pyruvate to glycerol.
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PMID:Glycerol synthesis in the rainbow smelt Osmerus mordax 932 Apr 97

The daily turnover of protein amounts to 280 g in an adult weighing 70 kg but the metabolic processes responsible for protein turnover are only just beginning to be understood. In cells, the major pathway of protein degradation is the ubiquitin-proteasome pathway and protein flux through this pathway is precisely regulated. In catabolic conditions such as uremia, activity of the ubiquitin-proteasome pathway increases, resulting in degradation of muscle protein. In addition to increased protein degradation, gene transcription is activated, resulting in higher levels of the mRNAs encoding ubiquitin and proteasome subunits. The signals activating this pathway include metabolic acidosis and glucocorticoids but must be more diverse since the pathway is also activated in response to starvation, sepsis, cancer, muscle denervation, thermal injury, and acute diabetes. Understanding how the pathway is controlled could lead to the prevention of muscle loss in uremia and other conditions.
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PMID:Cellular mechanisms controlling protein degradation in catabolic states. 938 15

Six amino acids are metabolized in resting muscle. They are leucine, isoleucine, valine, asparagine, aspartate, and glutamate. These amino acids provide the amino groups and probably the ammonia required for synthesis of glutamine and alanine, which are released in excessive amounts in the postabsorptive state and during ingestion of a protein-containing meal. Only leucine and part of the isolecine molecule can be oxidized in muscle as they are converted to acetyl-CoA. The other carbon skeletons are used solely for de novo synthesis of TCA-cycle intermediates and glutamine. The carbon atoms of the released alanine originate primarily from glycolysis of blood glucose and from muscle glycogen (about half each in resting conditions). After consumption of a protein-containing meal, BCAA and glutamate are taken up by muscle and their carbon skeletons are used for de novo synthesis of glutamine. About half of the glutamine released from muscle originates from glutamate taken up from the blood, both after overnight starvation, after prolonged starvation, and after consumption of a mixed meal. Glutamine produced by muscle is an important fuel and regulator of DNA and RNA synthesis in mucosal cells and immune system cells, and fulfils several other important functions in human metabolism. The alanine aminotransferase reaction functions to establish and maintain high concentrations of TCA-cycle intermediates in muscle during the first 10 min of exercise. The increase in concentration of TCA-cycle intermediates probably is needed to increase the flux of the TCA-cycle and meet the increased energy demand of exercise. A gradual increase in leucine oxidation subsequently leads to a carbon drain on the TCA-cycle in glycogen-depleted muscles, and may thus reduce the maximal flux in the TCA-cycle and lead to fatigue. Deamination of amino acids and glutamine synthesis present alternative anaplerotic mechanisms in glycogen-depleted muscles, but only allow exercise at 40-50% of Wmax. One-leg exercise leads to the net breakdown of muscle protein. The liberated amino acids are used for synthesis of TCA-cycle intermediates and glutamine. Today, the importance of this process in endurance exercise in the field (running or cycling) in athletes who ingest carbohydrates is not clear. It is proposed that the maximal flux in the TCA-cycle is reduced in glycogen-depleted muscles due to insufficient TCA-cycle anaplerosis, and that this presents a limitation for the maximal rate of fatty acid oxidation. Interactions between the amino acid pool and the TCA-cycle are suggested to play a central role in the energy metabolism of the exercising muscle.
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PMID:Muscle amino acid metabolism at rest and during exercise: role in human physiology and metabolism. 969 93

The aim of this study was to quantify the effect of oral refeeding on the synthesis of soluble and contractile proteins in skeletal muscles, and to evaluate to what extent diet components (carbohydrate, fat, amino acids), hormones (insulin, IGF-I, GIP), Ca2+ flux, polyamine synthesis, cyclooxygenase activity, and muscle innervation are related to activation of protein synthesis at the translational level following oral refeeding. Adult, weight-stable, non-growing mice (C57B1) were used in starvation/refeeding experiments with oral chow. Growing rats (150 g) were used in parenteral refeeding experiments. Protein synthesis was measured in vivo in mixed muscles (phenylalanine flooding), in phasic EDL muscles (in vitro), and in cultured L-6 muscle cells. Overnight starvation reduced synthesis of soluble proteins by 37 +/- 8% (from 0.242 +/- 0.025 to 0.151 +/- 0.009 microgram-1.mg-1) and contractile proteins by 55 +/- 6% (from 0.148 +/- 0.018 to 0.068 microgram-1.mg-1) (P < 0.01). Soluble proteins with a basic net charge were more sensitive to nutrition compared to neutral and acidic proteins. Somatostatin treatment before refeeding attenuated muscle protein synthesis by 15% (P < 0.02). Mechanical stimulation of the gastrointestinal tract (bulk feeding) did not activate protein synthesis in muscles, while i.v. or i.p. provision of nutrients did. Oral refeeding normalized rates of protein synthesis within 3 h (P < 0.01), independently of intact muscle innervation, Ca2+ flux, polyamine synthesis, and cyclooxygenase activity in the skeletal muscles, while it was dependent on a complete substrate composition of the oral diet. Our results support the hypothesis that amino acids, probably in concerted action with locally produced tissue IGF-I, stimulate protein synthesis in skeletal muscles during refeeding.
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PMID:The role of diet components, gastrointestinal factors, and muscle innervation on activation of protein synthesis in skeletal muscles following oral refeeding. 1031 56

Sarcopenia could result from the inability of an older individual to recover muscle lost during catabolic periods. To test this hypothesis, we compared the capacity of 5-day-refed 12- and 24-mo-old rats to recover muscle mass lost after 10 days without food. We measured gastrocnemius and liver protein synthesis with the flooding-dose method and also measured nitrogen balance, 3-methylhistidine excretion, and the gene expression of components of proteolytic pathways in muscle comparing fed, starved, and refed rats at each age. We show that 24-mo-old rats had an altered capacity to recover muscle proteins. Muscle protein synthesis, inhibited during starvation, returned to control values during refeeding in both age groups. The lower recovery in 24-mo-old rats was related to a lack of inhibition of muscle proteolysis during refeeding. The level of gene expression of components of the proteolytic pathways did not account for the variations in muscle proteolysis at both ages. In conclusion, this study highlights the role of muscle proteolysis in the lower recovery of muscle protein mass lost during catabolic periods.
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PMID:Lower recovery of muscle protein lost during starvation in old rats despite a stimulation of protein synthesis. 1051 19

A myosin-lacZ fusion, expressed in 103 muscle cells of Caenorhabditis elegans, reports on how proteolysis in muscle is controlled by neural and intramuscular signals. Upon acute starvation, the fusion protein is degraded in the posterior 63 cells of the body-wall muscle, but remains stable in 32 anterior body-wall muscles and 8 vulval muscle cells. This distinction correlates with differences in the innervation of these cells. Reporter protein in the head and vulval muscles becomes labile upon genetic 'denervation' in mutants that have blocks in pre-synaptic synthesis or release of acetylcholine (ACh) or post-synaptic reception at nicotinic ACh receptors (nAChR), whereas protein in all 103 muscles is stabilized by the nicotinic agonist levamisole in the absence of ACh production. Levamisole does not stabilize muscle protein in nAChR mutants that are behaviorally resistant to levamisole. Neural inputs thus exert negative control over the proteolytic process in muscle by stimulating muscle nicotinic ACh receptors.
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PMID:Genetic defects in acetylcholine signalling promote protein degradation in muscle cells of Caenorhabditis elegans. 1080 11


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