Modulation of fatty-acid-binding protein content of rat heart and skeletal muscle by endurance training and testosterone treatment

The effects of training and/or testosterone treatment and its aromatization to oestradiol on fatty-acid-binding protein (FABP) content and cytochrome c oxidase activity in heart, soleus and extensor digitorum longus (EDL) muscles were studied in intact adult female rats. One group of rats remained sedentary, whereas the others were trained for 7 weeks. Thereafter the trained rats were divided into control and testosterone-treated groups, with or without an aromatase inhibitor. Testosterone was administered by a silastic implant. Training was continued for 2 weeks. In untreated sedentary rats the immunochemically assayed FABP contents were 497±28, 255±49 and 58±17 g/g wet weight for the heart, soleus, and EDL respectively. In the heart the FABP content was increased after training (29%), testosterone treatment (33%) or both manipulations (53%). In soleus muscle FABP increased only after testosterone treatment (16%), whereas in EDL no changes were found. Inhibiting the aromatase enzyme complex abolished the testosterone-induced effect on FABP content in soleus (suggesting an oestradiol effect) but not in heart muscle. Among the three muscles studied the FABP content was found to be related to the cytochrome c oxidase activity in a non-linear way. In conclusion, it is shown that the FABP contents and mitochondrial activities of heart and skeletal muscle are affected by training and sex hormones and that these effects are different for heart and skeletal muscles.Established Investigator of the Netherlands Heart Foundation     

The effect of exercise training on glycogen,glycogen synthase and phosphorylase in muscle and liver

Summary It is thought that exercise training in both man and the rat results in a protective effect against the depletion of carbohydrate stores during exercise (glycogen-sparing). However there has been no comprehensive study of the effects of training on glycogen anabolic and catabolic enzymes with liver or muscle. The aim of this study was to examine whether changes in these enzymes occur and whether these changes may provide an explanation for the glycogen-sparing which results from exercise training.Male rats were trained by a treadmill running program at three different workloads. In addition, there were three control groups: free eating (SF), food restricted (SR), and one SF with a single bout of exercise prior to sacrifice.Exercise training was associated with a 60–150% increase in glycogen synthase and phosphorylase and a 50–70% increase in glycogen content in soleus, an intermediate muscle, but not in extensor digitorum longus (EDL), a white muscle nor in liver. The increase in glycogen synthase and phosphorylase in intermediate muscle was proportional to the degree of training and there was a significant correlation between glycogen content, glycogen synthase, and phosphorylase activity in intermediate muscle. Cytochrome c oxidase activity, an indicator of respiratory capacity, increased 50% in gastrocnemius of trained rats and was significantly correlated with glycogen synthase and phosphorylase in soleus.These results indicate a significant effect of exercise training on glycogen anabolic and catabolic enzymes in intermediate muscle, with no significant effects in white muscle or liver. The changes do not provide an explanation for glycogen-sparing, but are consistent with improved capacity of intermediate muscle for rapid glycogen mobilisation and repletion.     

Physiological and biochemical characteristics of skeletal muscles in sedentary and active rats

Laboratory rats are sedentary if housed in conditions where activity is limited. Changes in muscle characteristics with chronic inactivity were investigated by comparing sedentary rats with rats undertaking voluntary wheel running for either 6 or 12 weeks. EDL (type II fibers) and soleus (SOL) muscles (predominantly type I fibers) were examined. When measured within 1–2 h post-running, calcium sensitivity of the contractile apparatus was increased, but only in type II fibers. This increase disappeared when fibers were treated with DTT, indicative of oxidative regulation of the contractile apparatus, and was absent in fibers from rats that had ceased running 24 h prior to experiments. Specific force production was ~?10 to 25% lower in muscle fibers of sedentary compared to active rats, and excitability of skinned fibers was decreased. Muscle glycogen content was ~?30% lower and glycogen synthase content?~?50% higher in SOL of sedentary rats, and in EDL glycogenin was 30% lower. Na⁺, K⁺-ATPase α1 subunit density was ~?20% lower in both EDL and SOL in sedentary rats, and GAPDH content in SOL?~?35% higher. There were no changes in content of the calcium handling proteins calsequestrin and SERCA, but the content of CSQ-like protein was increased in active rats (by ~?20% in EDL and 60% in SOL). These findings show that voluntary exercise elicits an acute oxidation-induced increase in Ca²⁺ sensitivity in type II fibers, and also that there are substantial changes in skeletal muscle characteristics and biochemical processes in sedentary rats.     

Effect of different types of high carbohydrate diets on glycogen metabolism in liver and skeletal muscle of endurance-trained rats

Male Wistar rats were fed ad libitum four different diets containing fructose, sucrose, maltodextrins or starch as the source of carbohydrate (CH). One group was subjected to moderate physical training on a motor-driven treadmill for 10 weeks (trained rats). A second group received no training and acted as a control (sedentary rats). Glycogen metabolism was studied in the liver and skeletal muscle of these animals. In the sedentary rats, liver glycogen concentrations increased by 60%–90% with the administration of simple CH diets compared with complex CH diets, whereas skeletal muscle glycogen stores were not significantly affected by the diet. Physical training induced a marked decrease in the glycogen content in liver (20%–30% of the sedentary rats) and skeletal muscle (50%–80% of the sedentary rats) in animals fed simple (but not complex) CH diets. In liver this was accompanied by a two-fold increase of triacylglycerol concentrations. Compared with simple CH diets, complex CH feeding increased by 50%–150% glycogen synthase (GS) activity in liver, whereas only a slight increase in GS activity was observed in skeletal muscle. In all the animal groups, a direct relationship existed between tissue glucose 6-phosphate concentration and glycogen content (r = 0.9911 in liver, r = 0.7177 in skeletal muscle). In contrast, no relationship was evident between glycogen concentrations and either glycogen phosphorylase activity or adenosine 5-monophosphate tissue concentration. The results from this study thus suggest that for trained rats diets containing complex CH (compared with diets containing simple CH) improve the glycogenic capacity of liver and skeletal muscle, thus enabling the adequate regeneration of glycogen stores in these two tissues.     

Additivity of adrenaline and contractions on hormone‐sensitive lipase,but not on glycogen phosphorylase,in rat muscle

Aim: Hormone‐sensitive lipase (HSL) has been proposed to regulate triacylglycerol (TG) breakdown in skeletal muscle. In muscles with different fibre type compositions the influence on HSL of two major stimuli causing TG mobilization was studied. Methods: Incubated soleus and extensor digitorum longus (EDL) muscles from 70 g rats were stimulated by adrenaline (5.5 μm , 6 min) or contractions (200 ms tetani, 1 Hz, 1 min) in maximally effective doses or by both adrenaline and contractions. Results: Hormone‐sensitive lipase activity was increased significantly by adrenaline as well as contractions, and the highest activity (P < 0.05) was seen with combined stimulation [Soleus: 0.40 ± 0.03 (SE) m‐unit mg protein^?1 (basal), 0.65 ± 0.02 (adrenaline), 0.65 ± 0.03 (contractions), 0.78 ± 0.03 (adrenaline and contractions); EDL: 0.18 ± 0.01, 0.30 ± 0.02, 0.26 ± 0.02, 0.32 ± 0.01]. Glycogen phosphorylase activity was always increased more by adrenaline compared with contractions [Soleus: 60 ± 4 (a/a + b)% vs. 46 ± 3 (P < 0.05); EDL: 60 ± 5 vs. 39 ± 6 (P < 0.05)]. After combined stimulation glycogen phosphorylase activity in soleus [59 ± 3 (a/a + b)%] was identical to and in EDL [45 ± 4 (a/a + b)%] smaller (P < 0.05) than the activity after adrenaline only. Conclusions: In slow‐twitch oxidative as well as in fast‐twitch glycolytic muscle HSL is activated by both adrenaline and contractions. These stimuli are partially additive indicating at least partly different mechanisms of action. Contractions may impair the enhancing effect of adrenaline on glycogen phosphorylase activity in muscle.     

Effects of adrenaline infusion on cAMP and glycogen phosphorylase in fast-twitch and slow-twitch rat muscles

This study investigated the effect of adrenaline infusion on the cAMP content, glycogen phosphorylase activity and the rate of glycogen breakdown in rat extensor digitorum longus (EDL) and soleus muscles. Adrenaline was constantly infused in a dose of 0.15 micrograms kg-1 body wt min-1. The cAMP content increased approximately 2.8-fold in both muscles after 2 min of infusion. Phosphorylase a + b activity was six times higher in fast-twitch muscle (EDL) than in slow-twitch (soleus) and remained unchanged during the infusion. Phosphorylase a activity increased by 8.4-fold in EDL and 2.4-fold in soleus muscles during the infusion period. Glycogen content decreased in EDL muscle by 10% whereas no change was observed in soleus. It is concluded that beta-adrenergic stimulation by adrenaline results in a similar cAMP increase in both muscles. The low rate of glycogen breakdown in EDL and the unchanged content of glycogen in soleus muscle suggest that cAMP mediated transformation of phosphorylase b to a in itself is not adequate for a rapid glycogenolysis in muscle.     

Interaction of exercise and diet on GLUT‐4 protein and gene expression in Type I and Type II rat skeletal muscle

We determined the interaction of exercise and diet on glucose transporter (GLUT‐4) protein and mRNA expression in type I (soleus) and type II [extensor digitorum longus (EDL)] skeletal muscle. Forty‐eight Sprague Dawley rats were randomly assigned to one of two dietary conditions: high‐fat (FAT, n=24) or high‐carbohydrate (CHO, n=24). Animals in each dietary condition were allocated to one of two groups: control (NT, n=8) or a group that performed 8 weeks of treadmill running (4 sessions week^–1 of 1000 m @ 28 m min^–1, RUN, n=16). Eight trained rats were killed after their final exercise bout for determination of GLUT‐4 protein and mRNA expression: the remainder were killed 48 h after their last session for measurement of muscle glycogen and triacylglycerol concentration. GLUT‐4 protein expression in NT rats was similar in both muscles after 8 weeks of either diet. However, there was a main effect of training such that GLUT‐4 protein was increased in the soleus of rats fed with either diet (P < 0.05) and in the EDL in animals fed with CHO (P < 0.05). There was a significant diet–training interaction on GLUT‐4 mRNA, such that expression was increased in both the soleus (100% ↑P < 0.05) and EDL (142% ↑P < 0.01) in CHO‐fed animals. Trained rats fed with FAT decreased mRNA expression in the EDL (↓ 45%, P < 0.05) but not the soleus (↓ 14%, NS). We conclude that exercise training in CHO‐fed rats increased both GLUT‐4 protein and mRNA expression in type I and type II skeletal muscle. Despite lower GLUT‐4 mRNA in muscles from fat‐fed animals, exercise‐induced increases in GLUT‐4 protein were largely preserved, suggesting that control of GLUT‐4 protein and gene expression are modified independently by exercise and diet.     

Activation of glycogen phosphorylase by electrical stimulation of isolated fast-twitch and slow-twitch muscles from rat

The influence of muscle contraction, induced by electrical stimulation, on the activity of glycogen phosphorylase, the contents of high-energy phosphates, hexose-monophosphates and lactate have been studied in isolated extensor digitorum longus (EDL) and soleus muscles from rats. The activity of phosphorylase a + b was about nine times higher in fast twitch muscles (EDL) than in slow-twitch soleus and remained unchanged during the stimulation. A pronounced increase of phosphorylase a occurred during the stimulation in EDL muscle. Stimulation with a frequency of 50 Hz for 10 s and 2 Hz for 90 s resulted in a 44-fold and five-fold increase in phosphorylase a, respectively. In contrast, stimulation of soleus muscle resulted in only a minor increase of phosphorylase a. The rate of glycogenolysis increased in both muscles during the stimulation but the increase was four to five times higher in the EDL than in soleus muscle. The content of phosphocreatine (PCr) before stimulation was much higher in EDL than in soleus but similar after the stimulation. This resulted in a three- to four-fold higher release of inorganic phosphate (Pi) in EDL than in soleus during contraction. Pi has previously been shown to be present in a limiting amount for the activity of phosphorylase and the increase during contraction is of importance for increasing the glycogenolytic rate. It is concluded that the higher glycogenolytic capacity in fast-twitch muscles compared to slow-twitch muscles is due to: (1) higher content of phosphorylase a + b, (2) higher degree of transformation of the enzyme into the a form during contraction, and (3) higher content of PCr, which liberates a large amount of Pi during contraction.     

Effect of endurance training and/or fish oil supplemented diet on cytoplasmic fatty acid binding protein in rat skeletal muscles and heart

Endurance training and/or a fish oil supplemented diet affect cytoplasmic fatty acid binding protein (FABP_c) content in rat skeletal muscles and heart. After 8 weeks of swimming, trained rats exhibited higher FABP_c content in the extensor digitorum longus (EDL) and in the gastrocnemius than did control rats (30%). The FABP_c increase was associated with an increase of citrate synthase activity (85% and 93%, respectively, in the two muscles), whereas lactate dehydrogenase activity decreased significantly. In contrast, in the soleus and in the heart we did not observe any effect of exercise either on FABP_c or on the metabolic profile. Therefore, increasing oxidative capacities of muscle by exercise resulted in a concomitant increase of the FABP_c content. Giving a polyunsaturated fatty acid (ω-3) supplemented diet for eight weeks induced a large rise of the FABP_c in EDL (300%), gastrocnemius (250%), soleus (50%) and heart (15%) without a concurrent accumulation of intramuscular triglycerides or modification of the citrate synthase activity, suggesting that polyunsaturated fatty acids may increase FABP_c content by up-regulating fatty acid metabolism genes via peroxisome proliferator-activated receptor alpha activation. Endurance trained rats fed with an ω-3 diet had similar FABP_c content in the gastrocnemius muscle when compared to sedentary ω-3 fed rats, whereas an additive effect of exercise and diet was observed in the EDL. The FABP_c in the soleus and in the heart of rats fed with ω-3 supplements remained constant whether rats performed exercise or not. As a result, both exercise and ω-3-enriched diet influenced FABP_c content in muscle. These two physiological treatments presumably acted on FABP_c content by increasing fatty acid flux within the cell. Electronic Publication     

Additivity of adrenaline and contractions on hormone-sensitive lipase,but not on glycogen phosphorylase,in rat muscle

AIM: Hormone-sensitive lipase (HSL) has been proposed to regulate triacylglycerol (TG) breakdown in skeletal muscle. In muscles with different fibre type compositions the influence on HSL of two major stimuli causing TG mobilization was studied. METHODS: Incubated soleus and extensor digitorum longus (EDL) muscles from 70 g rats were stimulated by adrenaline (5.5 microm, 6 min) or contractions (200 ms tetani, 1 Hz, 1 min) in maximally effective doses or by both adrenaline and contractions. RESULTS: Hormone-sensitive lipase activity was increased significantly by adrenaline as well as contractions, and the highest activity (P < 0.05) was seen with combined stimulation [Soleus: 0.40 +/- 0.03 (SE) m-unit mg protein(-1) (basal), 0.65 +/- 0.02 (adrenaline), 0.65 +/- 0.03 (contractions), 0.78 +/- 0.03 (adrenaline and contractions); EDL: 0.18 +/- 0.01, 0.30 +/- 0.02, 0.26 +/- 0.02, 0.32 +/- 0.01]. Glycogen phosphorylase activity was always increased more by adrenaline compared with contractions [Soleus: 60 +/- 4 (a/a + b)% vs. 46 +/- 3 (P < 0.05); EDL: 60 +/- 5 vs. 39 +/- 6 (P < 0.05)]. After combined stimulation glycogen phosphorylase activity in soleus [59 +/- 3 (a/a + b)%] was identical to and in EDL [45 +/- 4 (a/a + b)%] smaller (P < 0.05) than the activity after adrenaline only. CONCLUSIONS: In slow-twitch oxidative as well as in fast-twitch glycolytic muscle HSL is activated by both adrenaline and contractions. These stimuli are partially additive indicating at least partly different mechanisms of action. Contractions may impair the enhancing effect of adrenaline on glycogen phosphorylase activity in muscle.     

Interaction of exercise and diet on GLUT-4 protein and gene expression in Type I and Type II rat skeletal muscle

We determined the interaction of exercise and diet on glucose transporter (GLUT-4) protein and mRNA expression in type I (soleus) and type II [extensor digitorum longus (EDL)] skeletal muscle. Forty-eight Sprague Dawley rats were randomly assigned to one of two dietary conditions: high-fat (FAT, n=24) or high-carbohydrate (CHO, n=24). Animals in each dietary condition were allocated to one of two groups: control (NT, n=8) or a group that performed 8 weeks of treadmill running (4 sessions week-1 of 1000 m @ 28 m min-1, RUN, n=16). Eight trained rats were killed after their final exercise bout for determination of GLUT-4 protein and mRNA expression: the remainder were killed 48 h after their last session for measurement of muscle glycogen and triacylglycerol concentration. GLUT-4 protein expression in NT rats was similar in both muscles after 8 weeks of either diet. However, there was a main effect of training such that GLUT-4 protein was increased in the soleus of rats fed with either diet (P < 0.05) and in the EDL in animals fed with CHO (P < 0.05). There was a significant diet-training interaction on GLUT-4 mRNA, such that expression was increased in both the soleus (100% upward arrowP < 0.05) and EDL (142% upward arrowP < 0.01) in CHO-fed animals. Trained rats fed with FAT decreased mRNA expression in the EDL ( downward arrow 45%, P < 0.05) but not the soleus ( downward arrow 14%, NS). We conclude that exercise training in CHO-fed rats increased both GLUT-4 protein and mRNA expression in type I and type II skeletal muscle. Despite lower GLUT-4 mRNA in muscles from fat-fed animals, exercise-induced increases in GLUT-4 protein were largely preserved, suggesting that control of GLUT-4 protein and gene expression are modified independently by exercise and diet.     

The effects of high-intensity exercise on skeletal muscle neutrophil myeloperoxidase in untrained and trained rats

The primary purpose of this study was to examine the effects of high-intensity acute exercise on neutrophil infiltration in different muscle fiber types of untrained rats and to compare postexercise neutrophil accumulation in muscles of untrained and trained animals. The effect of high-intensity acute exercise on blood neutrophil degranulation reaction in trained animals was also elucidated. Neutrophil enzyme myeloperoxidase (MPO) was determined as a measure of neutrophil migration into muscles and blood neutrophil degranulation. Male albino rats were subjected to acute exercise and 5 weeks of training. The used model of intensive acute exercise consisted of 5, 15, and 25 intermittent swimming bouts with the addition of weight (8% of total body mass) for 1-min each, followed by 1.5-min rest intervals. MPO was analyzed in quadriceps muscle (white and red portion) and in soleus muscle 24 h after acute exercise. MPO content in resting blood plasma and neutrophils was determined 48-h following the completion of a training process. In addition, MPO content in the trained rats was measured immediately (in blood plasma and neutrophils) after and 24 h (in muscles) following a single-bout of exercise to exhaustion. The remaining two-third of the trained animals were exposed to a single-bout of nonstop swimming with the addition of 6% body mass until exhaustion. These animals were sacrificed immediately and 24 h after loaded swimming to analyze leukocyte count, MPO content in blood plasma and neutrophils and in muscles, respectively. About 24 h after exercise MPO concentrations in the red portion of quadriceps muscle and in soleus muscle were 4–7-fold higher as compared to the white portion of m. quadriceps. There was an association between the quantity of repetitive bouts of swimming and MPO content in the muscles. The duration of swimming to exhaustion of trained rats was 3.8-fold longer than untrained sedentary control. At rest, plasma MPO concentration was found to be 40% higher in trained rats compared to untrained controls (P < 0.05). Postexercise plasma MPO concentrations were significantly higher both in untrained (+137%; P < 0.05) and trained (+81%; P < 0.05) rats compared to resting values. At rest neutrophil MPO concentration was found to be 33% lower in trained rats compared to untrained controls (P < 0.05). There were no significant differences in muscle MPO concentrations between untrained and trained rats at rest. A single-bout of exercise to exhaustion produced a greater increase in MPO content in untrained compared to trained rats. The data suggest that postexercise neutrophil infiltration is more intensive in red fibers types compared to white fiber types. A smaller neutrophil infiltration in muscles of trained animals after exhaustive exercise suggests a protective effect of previous training to muscle injury.Portions of this paper were presented by V. Morozov in 2003 at the 6th ISEI Symposium on Exercise Muscle Metabolism and Immune Function, Copenhagen.     

Histochemical and morphological observations on rat myocardium after exercise

Effects of seven levels of chronic physical activity on the metabolic and morphologic characteristics of left ventricular myocardium of adult male albino rats were investigated.Treatments included sedentary control; voluntary running; short-duration, high-intensity running; medium-duration, moderate-intensity running; long-duration, low-intensity running; electric stimulus control; and endurance swimming. Excluding the controls, the animals were trained 5 days per week for 8 consecutive weeks. Food and water were providedad libitum to them. Fifty-six animals comprised the final sample.Histochemical techniques were used to evaluate the relative glycogen, fatty acid, SDH and LDH concentrations in the cardiac fibers. Each stain was measured objectively, using a photometer. A Hematoxylin and Eosin stain was employed to rate morphologic features. These sections were evaluated subjectively on the basis of presence or absence of lesions.Physical training for 8 weeks was sufficient to produce metabolic adaptations in the rats. The trained animals gained 37.4 % less body weight than did the sedentary controls (P < 0.05). However, neither histochemical nor morphological changes had occurred to the hearts of these animals consequent to the 8 weeks training programs. Apparently, the myocardial tissues examined, from the trained animals, contain the enzymes, SDH and LDH, and the substrates, glycogen and fatty acids, in amounts greater than that needed to cope with the exercise stress afforded by these training programs.     

Alteration of regulatory enzyme activities in fast-twitch and slow-twitch muscles and muscle fibres in low-intensity endurance-trained rats

The effect of progressive, low-intensity endurance training on regulatory enzyme activities in slow-twitch (ST) and fast-twitch (FT) muscle fibres was studied in 32 rats. Of those rats 16 were trained on a treadmill at a running speed of 10m · min^–1 5 days a week over an 8-week period. Running time was progressively increased from 15 min to 2 h · day^–1. Of the rats 4 trained and 4 sedentary rats were also subjected to acute exhausting exercise. Enzyme activities of phosphofructokinase 1 (PFKI) from glycolysis, -ketoglutarate dehydrogenase (-KGDH) from the Krebs cycle and carnitine palmitoyltransferase (CPT I and II) from fatty acid metabolism in soleus, tibialis anterior and gastrocnemius muscles were measured in trained and sedentary rats. Enzyme activities of individual ST and FT fibres were measured from the freeze-dried gastrocnemius muscle of 8 trained and 8 sedentary rats. In the sedentary rats the activity of PFK1 in tibialis anterior and soleus muscles was 141% and 41% of the activity in gastrocnemius muscle, respectively. The activity of -KGDH in tibialis anterior and soleus muscles was 164% and 278% of the activity in gastrocnemius muscle, respectively. The activity of CPT I in tibialis anterior and gastrocnemius muscles were at the same level, but in soleus muscle the activity was 127% of that in mixed muscle. Endurance training increased enzyme activities of -KGDH and CPT I significantly (P < 0.05) in gastrocnemius muscle but not in soleus or tibialis anterior muscle. After training both -KGDH and CPT II activities were elevated significantly (P < 0.05) in the ST fibres of gastrocnemius muscle, whereas in FT fibres only -KGDH was increased. For PFK1 activity no significant change was observed in ST or FT fibres. After acute exercise, activities of mitochondrial enzymes -KGDH and CPT I tended to be elevated in all muscles. Thus, low-intensity endurance training induced significant peripheral changes in regulatory enzyme activities in oxidative and fatty acid metabolism in individual ST or FT muscle fibres.     

Effect of short-term exercise training on muscle glycogen in resting conditions in rats fed a high fat diet

Summary It has been reported that exercise training increases muscle glycogen storage in rats fed a high carbohydrate (CHO) diet in resting conditions. The purpose of this study was to examine whether a 3-week swimming training programme would increase muscle glycogen stores in rats fed a high-fat (FAT) diet in resting conditions. Rats were fed either the FAT or CHO diet for 7 days ad libitum, and then were fed regularly twice a day (between 0800 and 0830 hours and 1800 and 1830 hours) for 32 days. During this period of regular feeding, half of the rats in both dietary groups had swimming training for 3 weeks and the other half were sedentary. The rats were not exercised for 48 h before sacrifice. All rats were killed 2 h after their final meal (2030 hours). The glycogen contents in red gastrocnemius muscle, heart and liver were significantly higher in sedentary rats fed the CHO diet than in those fed the FAT diet. Exercise training clearly increased glycogen content in soleus, red gastrocnemius and heart muscle in rats fed the CHO diet. In rats fed the FAT diet, however, training did not increase glycogen content in these muscles or the heart. Exercise training resulted in an 87% increase of total glycogen synthase activity in the gastrocnemius muscle of rats fed the CHO diet. However, this was not observed in rats fed the FAT diet. The total glycogen phosphorylase activity in the gastrocnemius muscle of the rats of both dietary groups was increased approximately twofold by training. These results suggested that muscle glycogen was enhanced in rats fed the CHO diet and that the glycogen content of the muscle of rats fed the FAT diet was not increased by exercise training.     

Effect of aerobic training on 99mTc-methoxy isobutyl isonitrile (99mTc-sestamibi) uptake by myocardium and skeletal muscle: implication for noninvasive assessment of muscle metabolic profile

Aim: The effect of long‐term endurance training on skeletal muscle and myocardial uptake of ^99mTc‐sestamibi, a radiopharmaceutical accumulating in the mitochondria, was investigated. Methods: Twenty‐six Wistar rats were divided into a trained (5 days week^?1 endurance running for 14 weeks) and an untrained group. On completion of training, ^99mTc‐sestamibi was administered and, 2 h post‐injection, the myocardium and the soleus, extensor digitorum longus (EDL) and medial gastrocnemius (MG) muscles were removed for the measurement of cytochrome c oxidase (CCO) activity and ^99mTc‐sestamibi uptake. Tissue ^99mTc‐sestamibi kinetics was preliminarily studied in 16 other rats for up to 2 h post‐injection. Results: Two hours post‐injection ^99mTc‐sestamibi uptake was either stable (myocardium) or still rising (skeletal muscles). Both CCO activity and ^99mTc‐sestamibi uptake decreased in the same order (myocardium, soleus, EDL, MG) in the tissues examined. The CCO activity of the EDL and MG muscles was higher (P < 0.05) in the trained compared to the untrained group. ^99mTc‐sestamibi uptake in the soleus and EDL muscles was higher (P < 0.05) in the trained compared to the untrained rats, whereas the difference in MG was marginally significant (P = 0.06) in favour of the trained group. Conclusions: Long‐term endurance training, resulting in elevated skeletal muscle CCO activity, is also associated with a similar increase in ^99mTc‐sestamibi uptake. This finding suggests that ^99mTc‐sestamibi could be used in imaging assessment of skeletal muscle metabolism with possible applications in both clinical and sports medicine settings.     

Effects of Growth hormone on rat skeletal muscle after hindlimb suspension

To examine the effects of growth hormone (GH) on the preferential atrophy of the soleus muscle (SOL) occurring after hindlimb suspension (HS), two groups of male rats received daily injections of 2 IU · kg ^–1 body mass of recombinant human growth hormone (rhGH). Rats were either suspended by the tail for 21 days (HS-GH, n = 5) or nonsuspended (CGH, n=5). The effects of rhGH treatment on SOL and extensor digitorum longus muscles (EDL) were compared in two groups of animals receiving daily injections of saline, either suspended by the tail (HS-SA, n = 5) or nonsuspended (C-SA, n = 5). The results showed that the SOL hypertrophy in response to rhGH administration was mostly observed in C rats (+33%, P<0.01). This increase in muscle mass was correlated with a concomitant increase in the size of type I fibres (+21%, P<0.05). Although SOL mass decreased during HS in rhGH treated animals (–44%, P<0.001), the mean normalized mass of this muscle did not significantly differ between C-SA and HS-GH groups. A statistically significant increase in the absolute mass of EDL occurred with rhGH treatment in CGH (+12%, P<0.05). The HS-induced decrease in the percentage distribution of type I fibres in SOL was unaffected by the rhGH treatment. In addition, a decrease in the citrate synthase activity in the whole SOL was observed in the two groups of tail-suspended rats (–31%, P<0.05; –21%, P<0.05 in SA and GH animals, respectively). The activity of 3-hydroxyacyl coenzyme A dehydrogenase was enhanced by the rhGH treatment (P<0.05) with similar magnitude in both C (+25%) and HS rats (+24%). Therefore, GH prevented only slightly the atrophy of SOL, occurring after 21 days of HS. The effects of rhGH treatment appeared most effective in C rats, suggesting that HS impaired the growth-promoting effects of this hormone on skeletal muscle.     

Effects of ageing and exercise on soleus and extensor digitorum longus muscles of female rats.

The effects of ageing and of exercise on muscle mass, fiber cross-sectional area, and fiber type composition of a weight-bearing muscle, the soleus and a non-weight-bearing muscle, the extensor digitorum longus (EDL) were investigated in female Long-Evans rats. The animals were exercised by means of voluntary wheel running beginning at 4 months. Runners and sedentary controls were studied at 9 months and 27 months of age. In sedentary rats, the soleus muscle weighed 26% less, and the EDL weighed 19% less at age 27 months, than at 9 months. This decline in muscle mass was accounted for by a similar decrease in muscle fiber cross-sectional area. The wheel running resulted in significant hypertrophy of the soleus in both 9- and 27-month-old rats; as a consequence the 27-month-old runners had larger soleus muscles than the 9-month-old sedentary rats. The running did not prevent atrophy of the EDL in the old rats, but did increase the proportion of type IIa fibers. The exercise also increased the number of capillaries per fiber in the soleus muscles of both young and old rats. In conclusion, the finding that wheel running prevented atrophy with ageing of the weight-bearing soleus but not of the non-weight-bearing EDL emphasizes the specificity of exercise, and shows that exercise-induced muscle hypertrophy can be maintained in old age by appropriate exercise.     

Altered hepatic glycogen metabolism and glucoregulatory hormones during sepsis.

Levels of glucose, insulin, and glucagon in portal vein plasma and of liver glycogen and cyclic AMP and activities of glycogen synthase and phosphorylase in liver were assayed in control (CONT) rats and rats infected (INF) with Diplococcus pneumoniae. In INF rats compared with CONT rats, insulin and glucagon levels were higher (8,12,24 h). Activity of synthase I was lower (8, 12, 24 h) and of phosphorylase higher (12 and 24 h) in INF rats. Cyclic AMP levels were higher in INF rats at 12 and 24 h. Total synthase activity was lower in INF rats at 24 h. Glucose given intravenously increased glycogen less in INF than in CONT rats and activated synthase and inactivated phosphorylase in all animals except at 24 h in INF rats. However, in situ perfusion of the livers at 24 h with glucose in buffer decreased phosphorylase activities in all animals and increased synthase I activities in CONT but not INF rats.     

Improved insulin‐stimulated glucose uptake and glycogen synthase activation in rat skeletal muscles after adrenaline infusion: role of glycogen content and PKB phosphorylation

Aim: Effects of in vivo adrenaline infusion on subsequent insulin‐stimulated glucose uptake and glycogen synthase activation was investigated in slow‐twitch (soleus) and fast‐twitch (epitrochlearis) muscles. Furthermore, role of glycogen content and Protein kinase B (PKB) phosphorylation for modulation insulin sensitivity was investigated. Methods: Male Wistar rats received adrenaline from osmotic mini pumps (≈150 μg kg^?1 h^?1) for 1 or 12 days before muscles were removed for in vitro studies. Results: Glucose uptake at physiological insulin concentration was elevated in both muscles after 1 and 12 days of adrenaline infusion. Insulin‐stimulated glycogen synthase activation was also improved in both muscles. This elevated insulin sensitivity occurred despite the muscles were exposed to hyperglycaemia in vivo. After 1 day of adrenaline infusion, glycogen content was reduced in both muscles; insulin‐stimulated PKB ser⁴⁷³ phosphorylation was increased in both muscles only at the highest insulin concentration. After 12 days of adrenaline infusion, glycogen remained low in epitrochlearis, but returned to normal level in soleus; insulin‐stimulated PKB phosphorylation was normal in both muscles. Conclusion: Insulin‐stimulated glucose uptake and glycogen synthase activation were increased after adrenaline infusion. Increased insulin‐stimulated glucose uptake and glycogen synthase activation after adrenaline infusion cannot be explained by a reduction in glycogen content or an increase in PKB phosphorylation. The mechanisms for the improved insulin sensitivity after adrenaline treatment deserve particular attention as they occur in conjunction with hyperglycaemia.