Biomedical subjects
Publications and source records attributed to S M Hay.
The dietary administration of clenbuterol to young male rats has been shown to produce a muscle specific hypertrophic growth response. This paper demonstrates that the combined effect of drug treatment and hypertrophic stimulus induced by tenotomy produced an additive effect on muscle growth. This effect was demonstrated in terms of both muscle composition (protein and RNA) and fibre size.
The effect of propranolol on clenbuterol-induced changes in muscle fibre size and protein content were studied. Propranolol did not inhibit the ability of clenbuterol to stimulate protein accretion but reduced the increase in muscle fibre size. The compositional and physical characteristics of clenbuterol-induced muscle growth thus appeared to be separated by propranolol.
1. Studies have been made of the time-sequence of protein metabolic and hormonal changes following an abrupt increase in carbohydrate or fat intake. [3H]leucine and [14C]urea were infused for 72 h, via the aorta, into fourteen female pigs (30-38 kg body-weight). At 24 h after the start of the infusion their feed was either changed to one of two isonitrogenous diets containing additional starch (group BS, five animals) or fat (group BF, five animals), or remained unaltered (group BB, four animals). The distribution space of urea was measured by the dilution of a single dose of [14C]urea given both 48 h before and 48 h after the change in diet. The changes in the concentration and specific radioactivity of blood leucine were used to infer changes in protein turnover and those of plasma urea to measure total amino acid catabolism. The concentrations of blood glucose and plasma insulin and cortisol were also measured at approximately two-hourly intervals for the 48 h period following the change in diet. 2. Within 4 h of either change in diet blood leucine concentration was lowered and the leucine specific radioactivity was raised above that in group BB, but after 24 h both the concentration and specific radioactivity of leucine returned to values similar to those in group BB. Eventually the blood leucine specific radioactivity was slightly but not significantly reduced below that of group BB. 3. The addition of starch to the diet significantly reduced the synthesis and concentration of urea within 4 h but, although the addition of fat to the diet eventually lowered the urea concentration and synthesis, both changes were delayed for 18-24 h. 4. In group BS plasma glucose and insulin rose after the addition of starch, but after 24-36 h both returned to values that were the same as those in the animals that received the same diet throughout (group BB). The addition of fat to the diet altered neither blood glucose nor plasma insulin concentrations. The addition of either carbohydrate or fat to the diet eventually reduced plasma cortisol concentrations, but the change did not occur until 24 h after the change in diet. 5. The results suggest that alterations in non-protein energy supply exert their immediate effect on the degradation of whole-body protein. They do not exclude the possibility that these early changes may reflect opposing changes at different sites.(ABSTRACT TRUNCATED AT 400 WORDS)
Six groups of 5 male rats (starting body weight 109 g) were allowed free access to a conventional rat diet. At 4 hourly intervals, starting at 10.00 h muscle protein synthesis was measured. By relating the weights of the gastrocnemius and soleus muscles to the initial body weights of the animals (i.e., at 09.30, day 1), a linear increase in muscle weight throughout the day was demonstrated. The fractional rate of muscle protein synthesis varied from 16.8% per day to 20.3% per day in gastrocnemius muscle and from 17.9% per day and 22.1% per day in the soleus. It was calculated that the maximum error incurred in estimating daily muscle protein synthesis by extrapolation of the value at any one time was 6% in gastrocnemius and 9% in soleus. It is concluded that calculations of the average rate of muscle protein degradation based on the difference between the rates of synthesis and deposition are generally valid in rats allowed free access to an adequate diet.
Dietary administration of the growth promoter, clenbuterol, ameliorated denervation-induced atrophy in rat soleus muscles. In acutely denervated muscles the drug inhibited the appearance of atrophy, and in chronically denervated muscles the atrophy was almost fully reversed. Responses in slow twitch oxidative fibres were particularly marked.
Changes in fractional protein synthesis rates (FSR) of 4 tissues (muscle, liver, intestine and bone) were assessed in 2 groups of young pigs from weaning, 10 days postpartum, to one week later, after feeding equal amounts of dry diets at 2 levels of protein (15 and 30%). In the meantime, protein and energy balance measurements were performed on the whole body partitioned into 4 components (carcass, liver, digestive organs, other organs + blood). Whole body energy balances were strongly negative in both groups as a result of low metabolisable energy (ME) intakes and fat mobilization. Protein balance improved, with the increase in dietary protein, at the expense of additional body fat loss. Parallel to that, an increase in the efficiency of ME for protein deposition was noticed. With the lower protein intake, protein deposition remained significantly positive in digestive tissues but not in liver and carcass. Muscle and liver RNA: protein ratios decreased after weaning at rates consistent with the normal age-dependent variations regardless of diet. FSRs were directly related to protein intake and the high supply allowed these tissues to match the preweaning values. In contrast, intestine RNA: protein ratio did not change after weaning and FSR was increased in both groups, with a trend to a higher value with the lower protein supply. Bone RNA: protein ratio and FSR both decreased after weaning on the low-protein diet; the effect of increasing dietary nitrogen could not be assessed in this tissue. The most typical effect of underfeeding associated with early-weaning seems to be an exaggeration of the normal age-dependent increase in protein synthesis per unit of RNA, provided that an adequate protein diet is fed. The relevance of these findings to the variations in the ME efficiency for protein deposition needs further investigations.
1. Young rats were offered to appetite a semi-synthetic diet either alone or containing the beta 2-selective agonist clenbuterol (4-amino-alpha[t-butylamino)methyl]-3,5-dichlorobenzyl alcohol). 2. In female rats (starting weight 116g) the presence of the drug at daily doses greater than 10 micrograms/kg body-weight per d increased the growth of skeletal and cardiac muscle but had no stimulatory effect on the growth of the liver, gastrointestinal tract and kidney. 3. Male rats (starting weight 53 g) received clenbuterol at a daily oral dose of 200 micrograms/kg body-weight per d. Animals were slaughtered after 0, 4, 8, 11, 18, 21 and 25 d of treatment. At 4, 11, 21 and 25 d muscle protein synthesis was measured by the method of Garlick et al. (1980). Although clenbuterol increased the rate of protein and RNA accretion in gastrocnemius and soleus muscles, protein synthesis was not increased. 4. The results suggested that the drug had a rapid, perhaps direct, inhibitory effect on protein degradation. It is concluded that the growth-promoting effect of clenbuterol may be specific to muscle and that the drug may act in a novel manner which circumvents the physiological mechanisms responsible for the control of muscle growth.
Groups of young rats (100 g body wt.) were starved from 23:00 to 11:00 h. The animals were then infused intravenously with diluent or insulin at three different doses to achieve plasma insulin concentrations of 20, 50 and 150 microunits/ml. Before the start of the infusion, animals received a single intravenous injection of indomethacin (250 micrograms) or diluent. After 20 min of infusion, the rats were injected with a large amount of labelled phenylalanine and were killed 10 min later. Insulin produced a dose-dependent decrease in plasma glucose and a dose-dependent rise in protein synthesis in cardiac, gastrocnemius, plantaris and soleus muscles. Protein synthesis in the liver was unaffected by insulin. Indomethacin had no effect on plasma glucose concentrations, but blocked the insulin-induced rise in protein synthesis in cardiac, gastrocnemius and plantaris, but not in soleus muscle. The hormone also increased the plasma concentration of prostaglandin E2 and of prostaglandins F2 alpha and E2 in gastrocnemius and plantaris muscle. The results show close similarities to previous observations with isolated rabbit muscles in vitro and suggest that the involvement of arachidonic acid metabolism in the action of insulin on protein synthesis is of physiological significance.