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Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fasting energy metabolism was studied in infants to determine the rates of utilization of endogenous carbohydrate, fat, and protein in relation to length of fasting, glucose homeostasis, other circulating energy substrates and hormones, and severe depletion of energy reserves due to prior malnutrition. Five subjects about 1 yr of age were each studied before and after restoration of their energy reserves. Following 3 days of a standard maintenance intake of energy and protein, the subjects were fasted until glycogen oxidation became negligible. Total energy utilization, determined by hourly oxygen consumption, did not diminish as a result of fasting but was significantly less when malnourished than when recovered, 66 versus 79 kcal/kg/day. In all cases the major energy source shifted from oxidation of dietary carbohydrate and glycogen to oxidation of fat, determined from the respiratory quotient, until the oxidation of glycogen became negligible and fat provided 94% of energy in the malnourished subjects after 21 hr and 92% in the recovered subjects after 27 hr. Utilization of protein, determined from urinary nitrogen excretion, remained very low in the malnourished infants accounting for a maximum of 4% of energy, 103 mg N/kg/day, whereas after recovery, protein utilization doubled as a result of fasting, finally accounting for 7% of energy, 226 mg N/kg/day (p less than 0.005). Urea accounted for 60% of total urinary N in both groups and plasma urea increased correspondingly in the recovered but not in the malnourished subjects. Plasma glucose decreased to about 40 mg/100 ml in both groups as glycogen oxidation diminished. The maximum amount of glucose that could have been derived from dietary carbohydrate, glycogen, glycerol, and amino acids decreased over this time from about 6 to 1 mg/kg/min. Alanine declined in relation to glucose concentration and was not different in the two groups in spite of the difference in urea production. Glycerol free fatty acids, beta-hydroxybutyrate, and acetoacetate increased in both groups, but the latter three of these remained significantly less in the malnourished group. Insulin decreased rapidly and remained equally low in both groups. Urinary epinephrine increased in both groups and cortisol was elevated after fasting, while growth hormone did not increase significantly. It is concluded that fasting infants complete the transition from dietary carbohydrate to endogenous fat as the major energy source much faster than do adults, proportionate to relatively greater energy utilization. Severe wasting did not prevent energy homeostasis in spite of greatly depleted body fat. Oxidation of fat continued to provide virtually all of the fasting energy requirements, although ketosis was relatively less. Utilization of endogenous protein also increased as a result of fasting but, by contrast, provided only a very small fraction of total energy, and this was substantially diminished as a result of wasting, similar to what has been found in starved adults...
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PMID:Fasting metabolism in infants. I. Effect of severe undernutrition on energy and protein utilization. 41 21

To determine if pancreatic glucoregulatory hormones can be implicated in the glucose fall of pregnancy, we have measured plasma immunoreactive insulin and glucagon (IRI and IRG) in rats. Fed rats in midgestation show a rise in IRI without a corresponding increase in IRG. In late gestation, IRG rises significantly, but only enough to keep pace with a further rise in IRI. On a molar basis, IRI remains the predominant hormone despite a marked fall in blood glucose. After a 48-h fast IRI falls to comparably low levels in pregnant and virgin rats. A small rise in IRG is seen in virgin but not in pregnant rats despite frank hypoglycemia in the latter. Thus, IRG secretion in pregnancy is diminished relative to IRI in the fed state and fails to increase in the fasted state despite the stimulus of a lower glucose in both instances. To evaluate IRG secretory reserve, the IRG response to i.v. alanine was assessed in late gestation. In fed rats a greater IRG increase is seen in pregnancy; after fasting no difference is seen between pregnant and virgin rats. These results preclude an absolute deficiency in glucagon secretion. Pancreas hormone stores were alos measured in an effort to explain the altered secretory state. We find reciprocal changes in IRI and IRG content favoring IRG in midgestation and IRI in late gestation. Thus, pancreas hormone storage is altered in pregnancy but does not account for the changes in hormone secretion. Rather, pregnancy exerts an effect on the islet secretory process itself. Release of IRI is enhanced relative to IRG regardless of the blood sugar level. These observations suggest that in the pregnant rat circulating levels of insulin and glucagon may act to limit hepatic glucose output. Available evidence from the literature supports the concept of restrained glucose production. It is proposed that a lower blood glucose production. It is proposed that a lower blood glucose in rat pregnancy may be a lesser liability teleologically than would be the obligate nitrogen wasting which accompanies gluconeogenesis.
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PMID:Plasma glucagon and insulin in rat pregnancy. Roles in glucose homeostasis. 110 77

Facioscapulohumeral disease (FSHD), an inherited neuromuscular disorder, is characterized by progressive wasting of specific muscle groups, particularly the proximal musculature of the upper limbs; the primary defect in this disorder is unknown. We studied a patient with FSHD to determine whether the mitochondrial respiratory chain was functionally abnormal. Muscle biopsy revealed fiber atrophy with patchy staining for oxidative enzymes. Electron microscopy of a liver section showed many enlarged mitochondria with paracrystalline inclusions. Decreased oxidation of the respiratory substrates-alanine and succinate-in skin fibroblasts suggested a deficiency of complex III of the electron-transport chain; cytochrome c oxidase activity (complex IV) was in the normal range. Biochemical analysis of liver supported the fibroblast data, since succinate oxidase activity (electron-transport activity through complexes II-IV) was reduced, whereas complex IV activity was normal. Furthermore, analysis of the cytochrome spectrum in liver revealed typical peaks for cytochromes cc1 and aa3, whereas cytochrome b (a component of complex III) was undetectable. Southern blot analysis of fibroblast mtDNA revealed no major deletions or rearrangements. Our study provides the first documentation of a specific enzyme-complex deficiency associated with FSHD.
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PMID:Deficiency of complex III of the mitochondrial respiratory chain in a patient with facioscapulohumeral disease. 184 91

Protein synthesis and degradation and net uptake and release of amino acids and minerals were examined in the perfused hemicorpus of bilaterally nephrectomized and sham-operated control rats. Animals were studied 30 h after surgery. In comparison with controls, uremic rats had greater urea N appearance (net urea generation) and lower plasma and muscle concentrations of most amino acids. Muscle protein synthesis was not altered, but protein degradation was greater in uremic versus sham rats. There was greater net release of phenylalanine, tyrosine, alanine, total nonessential amino acids, total amino acids, potassium, and phosphorus from the perfused hemicorpus of uremic rats and greater release of citrulline from sham rats. ATP, creatine phosphate, cAMP, and activities of cathepsin B1, cathepsin D, and alkaline protease were not different in muscles of the uremic versus sham rats. Thus, in acutely uremic rats there is increased protein wasting in the hemicorpus due to enhanced protein degradation. The enhanced protein degradation does not appear to be due to increased muscle cathepsin B1, cathepsin D, or alkaline protease activities.
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PMID:Protein and amino acid metabolism in posterior hemicorpus of acutely uremic rats. 630 4

Because prominent skeletal muscle dysfunction and muscle wasting are seen in both chronic uremia and in primary hyperparathyroidism, and because markedly elevated parathyroid hormone levels occur in both disorders, potential effects of parathyroid hormone on skeletal muscle protein, amino acid, and cyclic nucleotide metabolism were studied in vitro using isolated intact rat epitrochlearis skeletal muscle preparations. Intact bovine parathyroid hormone and the synthetic 1-34 fragment of this hormone stimulated the release of alanine and glutamine from muscle of control but not from chronically uremic animals. This stimulation was dependent upon the concentration of parathyroid hormone added: At 10(5) ng/ml parathyroid hormone increased alanine release 84% and glutamine release 75%. Intracellular levels of alanine and glutamine were not altered by parathyroid hormone. Increasing concentrations of the 1-34 polypeptide decreased [(3)H]leucine incorporation into protein of muscles from both control and uremic animals. Using muscles from animals given a pulse-chase label of [guanido-(14)C]arginine in vivo, parathyroid hormone increased the rate of loss of (14)C label from acid-precipitable protein during incubation and correspondingly increased the rate of appearance of this label in the incubation media. Parathyroid hormone increased muscle cAMP levels by 140% and cGMP levels by 185%, but had no effect on skeletal muscle cyclic nucleotide phosphodiesterase activities as assayed in vitro. Adenylyl cyclase activity in membrane preparations from control but not uremic rats was stimulated by parathyroid hormone in a concentration-dependent fashion. However, no stimulation of guanylyl cyclase activity was noted by parathyroid hormone, although stimulation by sodium azide was present. Incubation of muscles with added parathyroid hormone produced a diminished responsiveness towards epinephrine or serotonin regulation of amino acid release and cAMP formation in the presence compared to the absence of parathyroid hormone. In the absence of parathyroid hormone, detectable inhibition of alanine and glutamine release was produced by 10(-9) M epinephrine, whereas in the presence of parathyroid hormone (1,000 ng/ml) inhibition of alanine and glutamine release required 10(-6) M or greater epinephrine. Resistance to cyclic AMP action as well as inhibition of cyclic AMP formation by parathyroid hormone was found. Preincubation of rat sarcolemma with 1-34 parathyroid hormone produced a decreased activity of the isoproterenol-stimulable adenylyl cyclase activity but there was no apparent change in the concentration of isoproterenol required for one-half maximal and maximal stimulation of the enzyme. These findings suggest that high levels of parathyroid hormone have direct effects on skeletal muscle protein, amino acid, and cyclic nucleotide metabolism in muscle of normal but not uremic animals. Treatment with these high levels of parathyroid hormone in vitro appears to reproduce in normal muscle, the metabolic deficits and loss of hormone responsiveness observed in muscle of chronically uremic animals. It is therefore possible that direct effects of parathyroid hormone on skeletal muscle may account in part for the muscle dysfunction and wasting of primary hyperparathyroidism and chronic uremia.
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PMID:Effects of parathyroid hormone on skeletal muscle protein and amino acid metabolism in the rat. 630 55

Protein synthesis and degradation and net uptake and release of amino acids and minerals were investigated in the perfused hemicorpus of acutely uremic and control Sprague-Dawley rats. Rats underwent bilateral nephrectomy or sham surgery and were studied 30 hr after surgery. The uremic rats displayed greater urea N appearance (net urea generation), lower plasma and muscle concentrations of most amino acids, and increased muscle protein degradation as compared to control rats. Muscle protein synthesis was slightly but not significantly decreased in the uremic animals. There was greater net release of phenylalanine, tyrosine, alanine, total nonessential amino acids, total amino acids, potassium and phosphorus from the perfused hemicorpus of uremic rats and greater release of citrulline from sham rats. Muscle ATP, creatine phosphate, cyclic-AMP, and activities of cathepsin B1, cathepsin D, and alkaline protease were not different in the uremic and sham rats. These data provide evidence that acutely uremic rats sustain increased muscle protein wasting which is due to enhanced protein degradation. The increased protein degradation does not appear to be due to enhanced activities of muscle cathepsin B1, cathepsin D or alkaline protease.
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PMID:Enhanced muscle protein degradation and amino acid release from the hemicorpus of acutely uremic rats. 636 19

Protein synthesis and degradation and net uptake and release of amino acids and minerals were investigated in the perfused hemicorpus of acutely uremic and sham-operated control Sprague-Dawley rats. Rats underwent bilateral nephrectomy or sham surgery and were studied 30 hours after surgery. The uremic rats displayed greater urea nitrogen appearance (net urea generation), lower plasma and muscle intracellular concentrations of most amino acids, and increased protein degradation in the hemicorpus as compared with control animals. Muscle protein synthesis was slightly but not significantly decreased in the uremic animals as compared with controls. There was greater net release of phenylalanine, tyrosine, alanine, total nonessential amino acids, total amino acids, potassium, and phosphorus from the perfused hemicorpus of uremic rats and greater release of citrulline from sham rats. Muscle ATP, creatine phosphate, and cyclic AMP, and muscle cathepsin B1, cathepsin D, and alkaline protease activities were not different in the uremic and control rats. These data provide evidence that acutely uremic rats have increased muscle protein wasting which is due to enhanced protein degradation. The cause of the increased muscle protein degradation is unknown.
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PMID:Effect of acute uremia on protein degradation and amino acid release in the rat hemicorpus. 658 68

1. 20 patients before surgery received enteral nutrition for three days (12 g nitrogen, 1800 Kcal). Nitrogen and urea excretions in urine during the second and third day were determined. Eleven patients had a negative nitrogen balance (-2,7 and -2,4 g/day). In these patients urea production rates were 21,1 and 20,1 g/day. An urea production rate exceeding 15 g urea/day is probable an indication for a protein catabolism. The reason for this catabolic state seems to be a decreased protein utilisation (49 and 47 percent) as the result of a metabolic stress situation. This metabolic stress was determined according the stress index (Bistrian). The patients were in a stress situation comparable to postoperative stress (+3,7 and +3,9). The determination of urea production rate and catabolic index seems a suitable tool for defining a catabolic state. 2. 3-met-histidine excretion in urine were measured in seven patients postoperatively. In different periods saline or aminoacids solutions (5% alanine) were infused. During alanine administration protein (+49%)--and 3-met-histidine excretions (+50%) increased. It is not possible to state a catabolic situation out of the 3-met-histidine excretion, because an increased excretion may result from a stimulated protein synthesis in muscle tissue or from an increased muscleprotein wasting. 3. Free amino acid pools in plasma and muscle tissue were analysed in patients with severe illness of liver and pancreas. The free amino acid pattern differed from healthy volunteers. In patients with liver disease significantly increased concentrations of phenylalanine, tyrosine and methionine were found. In patients with acute pancreatitis highly abnormal pattern of intracellular amino acids occurred with decreased concentrations of glutamine, cysteine, histidine, lysine, arginine and ornithine. The highly significant decreased concentrations of glutamine (p less than 0,01) indicate a catabolic situation of these patients. A quantification of the severity of the catabolic state out of amino acid concentrations is not possible.
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PMID:[Biochemical methods for the determination of a clinical protein catabolism]. 679 72

To evaluate the effect ketone bodies on protein metabolism beta-hydroxybutyrate was infused into healthy nonobese and obese subjects and insulin dependent diabetics in the postabsorptive state and into obese subjects after 3 days and 3-10 wks of starvation. In association with blood ketone increments of 1-2 mM, plasma alanine fell by 25-35% in all treatment groups. Furthermore, the hypoalaninemic effect of beta-hydroxybutyrate was equally demonstrable in fasted subjects, in whom alanine was already reduced. In association with repeated 12 hr infusions of beta-hydroxybutyrate in subjects fasted 5-10 wks, urinary nitrogen fell by 30%, returning to baseline after cessation of the infusions and paralleling the changes in plasma alanine. When endogenous ketonemia was produced by isocaloric carbohydrate restriction (less than 25 gm/day), protein ingestion was associated with a 40-50% greater increase in plasma branched chain amino acids as well as a reduced rise in plasma insulin. The enhanced rise in branched chain amino acids was attributable to decreased net utilization since intravenous leucine also produced a 40% greater elevation in plasma leucine after carbohydrate restriction. When nitrogen balance was compared during hypocaloric (400 Kcal) feeding of a pure protein diet and a mixed diet containing 50% protein and 50% carbohydrate, no significant differences were observed. Isocaloric replacement with carbohydrate failed to accentuate nitrogen wasting, despite a marked lowering of blood and urinary ketones. Our findings support the possibility that ketone bodies contribute to the reduction in proteolysis and decrease in muscle alanine release which characterizes prolonged starvation. However, when endogenous hyperketonemia is induced by carbohydrate restriction, plasma insulin declines and the disposal of ingested protein is impaired. Furthermore, the addition of carbohydrate during hypocaloric feeding reduces hyperketonemia, but does not enhance negative nitrogen balance. These observations suggest that dietary carbohydrate and insulin also promote nitrogen retention and that ketogenic, high protein diets do not confer a unique protein sparing advantage.
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PMID:The effect of ketone bodies and dietary carbohydrate intake on protein metabolism. 694 62

Rats bearing the Yoshida AH-130 ascites hepatoma, a cachectic rat tumour, showed signs of important muscle wasting with reduced muscle weights. This phenomenon was associated with a decreased rate of in vivo alanine oxidation as measured by the production of 14CO2 from [U-14C]alanine intragastrically administered. It was later found that the decreased amino acid oxidation was associated with a reduced uptake in skeletal muscle as measured in incubated soleus muscles, thus suggesting that the decreased in vivo oxidation is basically due to a reduced oxidation of the amino acid in skeletal muscle. The decrease in alanine oxidation in the tumour-bearing animals was also associated with higher circulating alanine concentrations in their blood. In addition, tumour-bearing rats presented a lower (26%) protein synthetic rate in skeletal muscle, as measured by the incorporation of [14C]phenylalanine into muscle protein. The addition of insulin to the incubation medium abolished the lower rate of protein synthesis, thus suggesting a greater response to this hormone by the muscle of tumour-bearing rats. In conjunction with a reduced protein synthesis, tumour-bearing rats showed a clearly enhanced rate of protein degradation in isolated skeletal muscles. The results presented confirm previous observations suggesting that the skeletal muscle of tumour bearing animals is in a profound negative nitrogen balance which partially accounts for the wasting observed in the tissue. In addition, the present study allows us to conclude that, in spite of the increased alanine utilization for both gluconeogenesis and tumour growth, the oxidation of alanine by the whole animal is decreased in the tumour-bearing rats. This seems to be associated with a decreased ability of skeletal muscle to handle this amino acid.
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PMID:Alanine metabolism in rats bearing the Yoshida AH-130 ascites hepatoma. 781 30


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