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Biomedical subjects

V R Preedy

Publications and source records attributed to V R Preedy.

At least 199 records · Page 11Linked to original sources
PubMed1988

The effect of chronic ethanol feeding on body and plasma composition and rates of skeletal muscle protein turnover in the rat.

(1) Sexually immature and mature rats were fed a nutritionally-complete liquid diet or isovolumetric quantities of the same diet in which 36% of the calories as glucose were substituted by isocaloric ethanol. (2) After 6 weeks ethanol feeding, significant reductions in body weight (approx. 15%) occurred in both groups of rats. In immature rats there were significant reductions (7-21%) in bone, gastrocnemius, liver, and skin weights. The total skeletal muscle mass was reduced by 20%. Lung and kidney weights were not significantly altered. In mature rats smaller decreases in organ weights were found, which were only significant for skeletal muscle and skin. The gastrocnemius protein content was significantly reduced in immature but not in mature rats. Plasma protein concentrations were unaltered in both groups. (3) Plasma aspartate aminotransaminase, gamma glutamyl transferase and creatine kinase activities in immature and mature rats were not significantly altered by ethanol feeding, but there were increases in plasma alkaline phosphatase activities in immature, but not in mature, rats. Plasma glucose was slightly raised by ethanol feeding in immature but not mature rats. Plasma triglycerides and insulin were unaltered in both groups of rats. (4) Protein synthesis was measured with a flooding dose of L[4(3)H]-phenylalanine. Rates of protein breakdown were calculated from the difference between synthesis and growth. Fractional and absolute rates of skeletal muscle protein synthesis were reduced by 13-30% by ethanol treatment, in immature and mature rats. Fractional rates of protein breakdown were also reduced by ethanol, by 13 and 19% in immature and mature rats, respectively.

Alanine Transaminase↗
PubMed1988

Biological effects of chronic ethanol consumption: a reappraisal of the Lieber-De Carli liquid-diet model with reference to skeletal muscle.

This paper responds to the recent article by Rao et al. (Alcohol and Alcoholism 21, 369-373, 1986) which suggested that the Lieber-De Carli liquid diet for chronic ethanol-feeding studies may not be suitable for the rat because of the changes in carbohydrate content. The viability of the Lieber-De Carli model was, therefore, re-examined. The content of the liquid diet was shown to be nutritionally adequate, when compared to a solid laboratory chow. However, rats on an alcohol feeding regime had sub-optimal growth rates, because of a reduction in the amount of liquid diet consumed. When compared to pair fed controls, rats fed the ethanol-containing diet showed marked changes in skeletal muscle. These observations are similar to those in man and we conclude that the use of the Lieber-De Carli feeding regime in experimental animals is a suitable means of investigating the mechanism of skeletal myopathy.

Alcoholism↗
PubMed1988

Comparison of the acute effects of ethanol on liver and skeletal muscle protein synthesis in the rat.

(1) The acute effects of ethanol on protein synthesis by liver and skeletal muscle were investigated in young (95-100 g) rats. Rats were injected intraperitoneally with ethanol, 75 mmol/kg body wt; controls were injected with isovolumetric 0.15 M NaCl. After 140 min rates of protein synthesis were measured by injection of a large dose of L[4(3)H]phenylalanine and at 150 min rats were killed. (2) Fractional rates of protein synthesis in control animals were approximately four to five times greater in liver than muscle. Absolute rates were, however, comparable in liver and skeletal muscle. Ethanol reduced the fractional rate of liver protein synthesis by 5-20%; the response for muscle was relatively greater (25-30%). The decrease in the amount of protein synthesized by muscle was also greater than that by liver. (3) After 150 min, plasma gamma-glutamyl transferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase and creatine kinase activities were all decreased by 25-60%. Aspartate aminotransferase activity was increased by 42%, though this was not statistically significant. (4) Increased plasma glucose and triglycerides in ethanol-dosed rats indicated that limitations in substrate supply were not mediating factors in reducing protein synthesis. Ethanol was also able to exert its effects in the presence of elevated insulin levels. A direct effect of ethanol, or its metabolites, on protein synthesis, is therefore implied.

Animals↗
PubMed1986

A comparison of rates of protein turnover in rat diaphragm in vivo and in vitro.

Protein synthesis and degradation rates in diaphragms from fed or starved rats were compared in vivo and in vitro. For fed rats, synthesis rates in vivo were approximately twice those in vitro, but for starved rats rates were similar. Degradation rates were less in vivo than in vitro in diaphragms from either fed or starved rats.

Animals↗
PubMed1986

The response of muscle protein synthesis to nutrient intake in postabsorptive rats: the role of insulin and amino acids.

In 12 h fasted rats, rates of muscle protein synthesis were stimulated by refeeding for 1 h and by intragastric or intravenous infusion of an amino acid plus glucose mixture for 1 hr, but not by intravenous infusion of amino acids alone for 1 h. Intravenous injection of anti-insulin serum suppressed the response to feeding and to intragastric infusion, but not to intravenous infusion. It is concluded that the response of muscle protein synthesis to food intake is mediated by both insulin and amino acids acting in concert.

Amino Acids↗
PubMed1985

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

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.

Amino Acids↗
PubMed1985

The effects of 6 hours of hypoxia on protein synthesis in rat tissues in vivo and in vitro.

Rates of protein synthesis were measured in vivo in several tissues (heart, skeletal muscles, liver, tibia, skin, brain, kidney, lung) of fed rats exposed to O2/N2 (1:9) for 6 h starting at 08:00-11:00 h. Protein synthesis rates were depressed by 15-35% compared with normoxic controls in all of the tissues studied. The decreases were greatest in the brain and the skin. Although hypoxia inhibited gastric emptying, its effects on protein synthesis could probably not be attributed to its induction of a starved state, because protein-synthesis rates in brain and skin were not decreased by a 15-18 h period of starvation initiated at 23:00 h. Furthermore, we showed that protein synthesis was inhibited by hypoxia in the rat heart perfused in vitro, suggesting a direct effect. The role of hypoxia in perturbing tissue nitrogen balance in various physiological and pathological states is discussed.

Animals↗
PubMed1985

Regional variation and differential sensitivity of rat heart protein synthesis in vivo and in vitro.

In vivo, fractional rates of protein synthesis in atrial muscle of hearts taken from fed rats were 70% greater than in ventricular muscle. After 3 days starvation, atrial protein synthesis is inhibited, but the inhibition is less than in ventricles. A crude subcellular fractionation of the aqueous homogenates by centrifugation at 32000g showed that the supernatant and precipitate proteins were synthesized at the same rate in the ventricles. The fractional rates of protein synthesis and RNA/protein ratios in the right ventricle were 10% greater than in the left ventricle. Protein synthesis in both of these regions was inhibited equally by starvation. In vitro, rates of protein synthesis in atria and ventricles of anterogradely perfused rat hearts were stimulated by saturating insulin concentrations and were inhibited by starvation, but the effects in atria were smaller than in ventricles. Rates of protein synthesis in atria in vitro were 80-95% of rates in vivo. The heart therefore shows considerable regional variation in rates of protein synthesis in vivo and in vitro, and the sensitivity of protein synthesis in the various regions to interventions such as insulin and starvation differs.

Animals↗
PubMed1984

Rates of protein turnover in vivo and in vitro in ventricular muscle of hearts from fed and starved rats.

Starvation of 300 g rats for 3 days decreased ventricular-muscle total protein content and total RNA content by 15 and 22% respectively. Loss of body weight was about 15%. In glucose-perfused working rat hearts in vitro, 3 days of starvation inhibited rates of protein synthesis in ventricles by about 40-50% compared with fed controls. Although the RNA/protein ratio was decreased by about 10%, the major effect of starvation was to decrease the efficiency of protein synthesis (rate of protein synthesis relative to RNA). Insulin stimulated protein synthesis in ventricles of perfused hearts from fed rats by increasing the efficiency of protein synthesis. In vivo, protein-synthesis rates and efficiencies in ventricles from 3-day-starved rats were decreased by about 40% compared with fed controls. Protein-synthesis rates and efficiencies in ventricles from fed rats in vivo were similar to values in vitro when insulin was present in perfusates. In vivo, starvation increased the rate of protein degradation, but decreased it in the glucose-perfused heart in vitro. This contradiction can be rationalized when the effects of insulin are considered. Rates of protein degradation are similar in hearts of fed animals in vivo and in glucose/insulin-perfused hearts. Degradation rates are similar in hearts of starved animals in vivo and in hearts perfused with glucose alone. We conclude that the rates of protein turnover in the anterogradely perfused rat heart in vitro closely approximate to the rates in vivo in absolute terms, and that the effects of starvation in vivo are mirrored in vitro.

Animals↗
PubMed1984

The metabolic state of muscle in the isolated perfused rat hemicorpus in relation to rates of protein synthesis.

Measures of perfusion adequacy in perfused rat hemicorpus preparations were investigated as potential indices of tissue function during studies of muscle protein metabolism. Perfusion under normal conditions for up to 80 min resulted in rates of protein synthesis and concentrations of ATP in muscle that were similar to those in vivo, but phosphocreatine in muscle gradually decreased and muscle lactate increased. Hypoxic conditions led to lower rates of protein synthesis, lower phospho-creatine and raised lactate contents in muscle compared with normal perfusions, and ATP was slightly decreased. Hypoxic preparations also released more lactate and K+ into the medium and had higher perfusion pressures, but glucose uptake and muscle water content were not altered. In totally ischaemic muscle, concentrations of ATP and phosphocreatine were even lower than in hypoxic muscle, and that of lactate was higher. From 11 preparations perfused for 60 min under normal conditions, three were selected on the basis of lower muscle ATP content than the others. Preparations with low ATP also showed lower muscle phosphocreatine concentrations, O2 uptake and CO2 output, as well as higher perfusion pressure and muscle lactate concentrations than in the remaining preparations, but muscle water, ADP and AMP concentrations and lactate and K+ flux were no different. In perfusions extended to 3 h, deterioration of function was more apparent. There were significant correlations between rates of protein synthesis and the concentrations of ATP, phosphocreatine and lactate in two different muscles (r = 0.756-0.929), but not with any of the other indices investigated. Taken overall, these experiments showed that concentrations of ADP, AMP and water in muscle, rates of lactate and glucose metabolism, K+ output, perfusion pressure and blood gas parameters were unsuitable for distinguishing unsound from sound preparations, because they did not consistently demonstrate differences, or could not be ascribed to only muscle metabolism. It was found that ATP, phosphocreatine and lactate concentrations in muscle were the best indicators of impaired metabolic state in studies of protein synthesis. Measurements of these could be used on a routine basis for rejecting unsatisfactory preparations.

Adenine Nucleotides↗
PubMed1983

Protein synthesis in skeletal muscle of the perfused rat hemicorpus compared with rates in the intact animal.

The rate of protein synthesis was measured in muscles of the perfused rat hemicorpus, and values were compared with rates obtained in whole animals. In gastrocnemius muscle of fed rats the rate of synthesis measured in the hemicorpus was the same as that in the whole animal. However, in plantaris, quadriceps and soleus muscles rates were higher in the hemicorpus than those in vivo. In the hemicorpus, starvation for 1 day decreased the rate of protein synthesis in gastrocnemius and plantaris muscles, in parallel with decreases in the RNA content, but the soleus remained unaffected. Similar effects of starvation were observed in vivo, so that the relationships between rates in vivo and in the hemicorpus were the same as those in fed rats. Proteins of quadriceps and plantaris muscles were separated into sarcoplasmic and myofibrillar fractions. The rate of synthesis in the sarcoplasmic fraction of the hemicorpus from fed rats was similar to that in vivo, but synthesis in the myofibrillar fraction was greater. In the plantaris of starved rats the rates of synthesis in both fractions were lower, but the relationships between rates measured in vivo and in the perfused hemicorpus were similar to those seen in fed rats. The addition of insulin to the perfusate of the hemicorpus prepared from 1-day-starved animals increased the rates of protein synthesis per unit of RNA in gastrocnemius and plantaris muscles to values above those seen in fed animals when measured in vivo or in the hemicorpus. Insulin had no effect on the soleus. Overall, the rates of protein synthesis in the hemicorpus differed from those in vivo. However, the effect of starvation when measured in the whole animal was very similar to that measured in the isolated rat hemicorpus when insulin was omitted from the perfusate.

Adenine Nucleotides↗
PubMed1983

The effect of insulin infusion and food intake on muscle protein synthesis in postabsorptive rats.

1. Insulin was infused into young male rats in the postabsorptive state. Rates of protein synthesis in skeletal muscle were determined during the final 10 min of infusion from the incorporation of label into protein after intravenous injection of a massive dose of [3H]phenylalanine. Rates of synthesis were not altered during the first 10 min of insulin infusion, but were increased significantly between 10 and 60 min. 2. Rats were infused with different amounts of insulin for 30 min. When concentrations were increased from 10 to 40 microunits/ml of plasma there was no change in muscle protein synthesis, but concentrations higher than 70 microunits/ml caused a significant stimulation. Concentrations below 10 microunits/ml, obtained by infusion of anti-insulin serum, did not depress synthesis below that found in the postabsorptive rat. 3. Infusion of glucose for 30 or 60 min led to an increase in plasma insulin to 40 microunits/ml, but this also failed to stimulate muscle protein synthesis. 4. Rates of synthesis in postabsorptive rats, even when stimulated maximally by insulin, were not so high as those in fed rats or in postabsorptive rats refed for 60 min. However, in fed and refed rats insulin concentrations were below that required to stimulate synthesis in postabsorptive animals. Despite this, infusion of large amounts of insulin into fed rats did not increase synthesis further. 5. The sensitivity of plasma glucose to insulin infusion was different from that of protein synthesis. A decrease in glucose concentration preceded the increase in synthesis and occurred at lower insulin concentrations. 6. It is concluded that changes in circulating insulin may have been partly responsible for the increase in muscle protein synthesis brought about by feeding, but that other factors must also play a part.

Animals↗
PubMed1983

Protein synthesis in skin and bone of the young rat.

Fractional rates of protein synthesis in tissues of young growing rats were estimated by injection of flooding amounts (1.5 mmol/kg body-weight) of [3H]phenylalanine. Rates of 63.6%/d and 90.4%/d respectively were obtained in the skin and bone (tibia) of fed animals. These rates were comparable to that in liver (86.3%/d) but considerably higher than in muscle (16.9%/d). Absolute amounts of protein synthesized in tissues of fed rats were estimated. Together the skin and bones accounted for 25% of whole-body synthesis, a value similar to the contribution of liver (15%) and muscle (25%). In fed rats the ratio, RNA:protein in skin and bone was lower than in liver, but much higher than in muscle. However, the amounts of protein synthesized per unit RNA in skin and bone were higher than in both liver and muscle. After 2 d of starvation the fractional rates of protein synthesis in skin and bone fell by 26% and 31% respectively. This was greater than the fall in liver (17%) but less than in muscle (66%). In bone the fall in synthesis was accompanied by decreases in both RNA:protein and synthesis per unit RNA, but in skin there was a fall in RNA:protein which was partially countered by an increase in the rate of synthesis per unit RNA.

Animals↗
PubMed1981

Rates of protein synthesis in skin and bone, and their importance in the assessment of protein degradation in the perfused rat hemicorpus.

The perfused rat hemicorpus preparation, which has frequently been used to study muscle metabolism, contains 39% by weight of non-muscle tissue such as skin and bone. Both the concentration of RNA and the incorporation of [U-14C]tyrosine into protein indicate that the non-muscle components are more active in protein synthesis than is muscle. These observations have important implications for studies of amino acid metabolism, and in particular for the measurement of muscle protein degradation in the hemicorpus.

Animals↗
PubMed1980

A rapid and convenient technique for measuring the rate of protein synthesis in tissues by injection of [3H]phenylalanine.

A rapid procedure for measuring the specific radioactivity of phenylalanine in tissues was developed. This facilitates the accurate determination of rates of protein synthesis in a wide range of tissues by injection of 150 mumol of L-[4-(3)H]phenylalanine/100 g body wt. The large dose of amino acid results in a rapid rise in specific radioactivity of free phenylalanine in tissues to values close to that in plasma, followed by a slow but linear fall. This enables the rate of protein synthesis to be calculated from measurements of the specific radioactivity of free and protein-bound phenylalanine in tissues during a 10 min period after injection of radioisotope.

Animals↗