Tumor necrosis factor‐alpha antagonist administration recovers skeletal muscle dysfunction in ovariectomized rats

Skeletal muscles deteriorate after ovariectomy. Molecular pathway of this deterioration has not been defined. Tumor necrosis factor (TNF)‐alpha activation is assumed to trigger muscle atrophy and administration of its antagonist is hypothesized to recover this atrophy in rats. Slow‐twitch soleus and fast‐twitch extensor digitorum longus muscle functions were investigated in intact, ovariectomized (OVX), and OVX plus 10 µg/g/week TNF‐alpha antagonist administered female rats. Maximum isometric twitch and tetanic contraction responses were lower in the OVX groups. Maximum isometric twitch amplitudes recovered in the extensor digitorum longus but not in the soleus muscles after TNF‐alpha antagonist administration. The decrease in responses to tetanic stimulations recovered in the OVX–TNF group at frequencies higher than 20 Hz in both muscle types. OVX animals body weight was 21% higher than intact animals. Muscle weight to body weight ratios of the OVX groups were higher than the control group which recovered after TNF‐alpha antagonist administration. Findings suggest that the functional loss in OVX rat muscles is TNF‐alpha pathway dependent. Skeletal muscle atrophy and function after OVX recovered by TNF‐alpha antagonist administration. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:275–280, 2011     

中枢神经提取液对失神经肌肉的作用

目的：研究中枢神经的有效物质对失神经肌肉的作用。方法：在ＳＤ大鼠失神经趾长伸肌中，应用中枢神经提取液（ｃｅｎｔｒａｌｎｅｒｖｅｅｘｔｒａｃｔ，ＣＥ），并观察肌肉萎缩的生理学指标。结果：肌肉失神经后的最大强直收缩力（ｔｅｔａｎｉｃｔｅｎｓｉｏｎ，ＰＯ）及强直收缩后动作电位（ｐｏｓｔｅｔａｎｉｃｔｗｉｔｃｈｐｏｔｅｎｔｉａｔｉｏｎ，ＰＴＰ）下降，舒张期时程（ｒｅｌａｘａｔｉｏｎｔｉｍｅ，ＲＴ）延长，肌湿重、肌肉总蛋白及肌纤维截面积（ｃｒｏｓｓ－ｓｅｃｔｉｏｎａｒｅａ，ＣＳＡ）的减少，均可被中枢神经提取液有效地缓解。结论：中枢神经提取液可减缓失神经肌肉的萎缩     

COMPARISON OF THE EFFECTS OF PANCURONIUM AND TUBOCURARINE ON DIFFERENT MUSCLES OF YOUNG AND OLD MICE

In order to evaluate the sensitivity of different muscle typesto neuromuscular blocking drugs, a system using mouse musclesin vitro was developed and applied to detect changes in drugsensitivity in relation to age. The effect of pancuronium andtubocurarine on initial twitch and on the ratio of fourth twitchto first twitch (T4/T1) of a train-of-four at 2 Hz were comparedin fast-twitch, slow-twitch and respiratory muscles in the mouse.The muscles used were: extensor digitorum longus (EDL), soleus(SOL) and diaphragm (DIA). For both drugs the order of decreasingsensitivity was EDL > SOL > DIA. This result was the samewhether first twitch or T4/T1 was used, although the latterwas a more sensitive indicator. The sensitivity of neuromuscularblock was less in muscles from old (30–33 month) animalsthan in the equivalent muscles from young (8–12 month)animals.     

Stiffness and muscle function with age and reduced muscle use.

Changes in passive muscle stiffness with age and disuse were assessed in male Fischer-344 and Brown Norway rats. Three groups of rats were studied: young (approximately 7 months old), old (approximately 33 months old), and old that had undergone 2 weeks of hindlimb unweighting, a model of reduced muscle use. Four hindlimb muscles were examined: the soleus (postural), plantaris (locomotor), extensor digitorum longus (nonpostural), and peroneus longus (nonpostural). Supramaximal stimuli elicited peak tetanic tensions throughout the available range of motion (amount of muscle elongation before the maximal attainable contractile or tetanic tension is obtained) for each muscle, permitting the creation of length-tension curves. Passive tension (amount encountered at each millimeter of change in muscle length) was also recorded throughout the available range of motion and was unchanged with aging and unchanged or reduced with hindlimb unweighting; muscle stiffness remained unchanged under both conditions. Passive tension, however, accounted for a greater proportion of total tension with age and particularly with hindlimb unweighting. A significant loss in muscle range of motion, resulting in a leftward shift in the length-tension curve, occurred with aging in only the plantaris. Hindlimb unweighting resulted in a marked loss in muscle range for all four muscles studied, suggesting that the remaining muscle force was constrained to a very small arc. Significant declines in muscle mass and peak contractile tension, associated with age and hindlimb unweighting, were observed for all four muscles.     

The Effects of d-Tubocurarine, Pancuronium and Atracurium on the Responses of Gastrocnemius and Soleus Muscles in the Cat

In vivo, the effects of d-tubocurarine (0.20 mg kg-1), pancuronium (0.015 mg kg-1) and atracurium (0.15 mg kg-1) on the responses of the indirectly stimulated cat gastrocnemius (fast) and soleus (slow) muscles to a twitch, train-of-four and tetanic stimuli were studied. The soleus muscle demonstrated a greater degree of fade than the gastrocnemius in response to tetanic stimuli (50 Hz). There was no difference between the responses of the two muscles to twitch or train-of-four stimuli with any of the drugs. Recovery of train-of-four ratio occurred more rapidly than did the tetanic fade ratio. At a time when train-of-four ratio exceeded 0.7, tetanic fade was still evident, especially in the soleus muscle.     

Vibration-induced muscle injury. An experimental model and preliminary findings.

The hind paws of rats were subjected to vibration at a frequency of 80 Hz., an acceleration of 32 m./s.2 rms (i.e. ah.w approximately 6.3 m./s.2 rms) for five hours daily during five consecutive days. Morphological, histochemical and immunohistochemical analyses of the soleus, extensor digitorum longus and the plantar muscles in the vibrated limb and the contralateral control limb were performed. No changes were seen in the soleus or extensor digitorum longus muscles but different degrees of degeneration of the muscle fibres were seen in the plantar muscle sections as well as signs of regeneration. No changes were observed in the contralateral unexposed limb. It is concluded that it is not only nervous tissue but also muscle tissue that can be affected by vibration. The changes seem to be confined to muscles close to the vibration exciter.     

A scanning electron microscopical and morphometrical analysis of neuromuscular junctions in different muscle fiber types in the zebra finch and rat

The differences of neuromuscular junctions (NMJs) between different muscle fibers had been examined with scanning electron microscopy and analyzed morphometrically. The anterior and posterior latissimus dorsi muscles of the zebra finch were compared. The former consisted exclusively of slow tonic fibers and the latter of fast twitch fibers. The former had numerous, small NMJs. The synaptic depressions were small in number. The latter had a large NMJ. The synaptic depressions were large in number, and subsynaptic folds were found. The extensor digitorum longus and soleus muscles in the rat were also compared. The former consisted mostly of fast twitch fibers whereas the latter consisted of slow twitch fibers (75%) and fast twitch fibers (25%). NMJ of slow twitch fiber was small and the subsynaptic folds had sparse, narrow slit-like and pit-like openings. NMJ of fast twitch fiber was large and the subsynaptic folds had numerous, wide and slit-like openings.     

Atropine sulphate enhances neuromuscular transmission in the rat

The effect of atropine (0.001-10 mumol.l-1) on neuromuscular transmission in the rat hemidiaphragm preparation was investigated by analysing its effects on directly and indirectly-elicited twitch, tetanic, post-tetanic twitch responses and on the phenomenon of post-tetanic twitch potentiation. The effect of atropine on contractions produced by endogenous acetylcholine (ACh) or exogenous ACh (added directly into organ bath containing muscle) was studied in rat ileum. The results showed that atropine in low concentrations (1 mumol.l-1 or less), enhanced the indirectly-elicited twitch, tetanic and post-tetanic twitch responses in the rat diaphragm preparation. The mean EC50 value of atropine-induced increase in twitch tension was 0.08 +/- 0.01 mumol.l-1 (mean +/- s.e. mean, n = 6). Atropine had little effect on directly-elicited twitch tension, but in high concentrations (10 mumol.l-1 or more), it reduced the directly, and indirectly-elicited twitch contractions and produced a neuromuscular block in the rat diaphragm preparation. Atropine increased the contraction produced, in rat ileum, by endogenous ACh, i.e. ACh released from the phrenic nerve stimulated at 50 Hz for 20 s duration (control contraction: 1.3 +/- 0.1 g, contraction in atropine: 1.7 +/- 0.2 g). In contrast, atropine significantly reduced the contraction produced by exogenous ACh in the same preparation (control contraction: 3.0 +/- 0.5 g, atropine: 2.0 +/- 0.1 g), suggesting that a different mechanism may be involved in the latter effect of atropine. It was concluded that atropine, in low concentration, enhanced neuromuscular transmission, possibly via a presynaptic mechanism. In high concentration, atropine may reduce and then block transmission, possibly via pre- and postsynaptic mechanisms.     

Insulin protects against muscle proteolysis induced by septic plasma

Sepsis, like trauma, causes proteolysis of skeletal muscle. Insulin normally protects against muscle protein degradation. In earlier work using a rat muscle preparation, insulin inhibition of proteolysis decreased in the presence of plasma from injured patients. The current experiments tested the effect of plasma from septic patients on insulin inhibition in the same model. The mean value of protein degradation among eight septic plasma samples was 49% greater than the mean value among five normal plasma samples in soleus muscle and 45% greater in extensor digitorum longus muscle. In the presence of insulin, 10(3) mU/L, the increases in degradation with septic plasma were 42% in soleus muscle and 48% in extensor digitorum longus muscle. Insulin reduced degradation an average of 6% (soleus) and 10% (extensor digitorum longus) in normal plasma and 10% (soleus) and 8% (extensor digitorum longus) in septic plasma. In contrast to results of other studies, these experiments show that the protective effect of a moderate concentration of insulin in resisting muscle protein degradation is not significantly different in the muscle protein degradation is not significantly different in the presence of septic human plasma compared with normal plasma. This finding supports clinical efforts to decrease proteolysis in septic patients by the administration of insulin.     

Activation of p38 mitogen-activated protein kinase alpha and beta by insulin and contraction in rat skeletal muscle: potential role in the stimulation of glucose transport

The stress-activated p38 mitogen-activated protein kinase (MAPK) was recently shown to be activated by insulin in muscle and adipose cells in culture. Here, we explore whether such stimulation is observed in rat skeletal muscle and whether muscle contraction can also affect the enzyme. Insulin injection (2 U over 3.5 min) resulted in increases in p38 MAPK phosphorylation measured in soleus (3.2-fold) and quadriceps (2.2-fold) muscles. Increased phosphorylation (3.5-fold) of an endogenous substrate of p38 MAPK, cAMP response element binder (CREB), was also observed. After in vivo insulin treatment, p38 MAPKalpha and p38 MAPKbeta isoforms were found to be activated (2.1- and 2.4-fold, respectively), using an in vitro kinase assay, in immunoprecipitates from quadriceps muscle extracts. In vitro insulin treatment (1 nmol/l over 4 min) and electrically-induced contraction of isolated extensor digitorum longus (EDL) muscle also doubled the kinase activity of p38 MAPKalpha and p38 MAPKbeta. The activity of both isoforms was inhibited in vitro by 10 micromol/l SB203580 in all muscles. To explore the possible participation of p38 MAPK in the stimulation of glucose uptake, EDL and soleus muscles were exposed to increasing doses of SB203580 before and during stimulation by insulin or contraction. SB203580 caused a significant reduction in the insulin- or contraction-stimulated 2-deoxyglucose uptake. Maximal inhibition (50-60%) occurred with 10 micromol/l SB203580. These results show that p38 MAPKalpha and -beta isoforms are activated by insulin and contraction in skeletal muscle. The data further suggest that activation of p38 MAPK may participate in the stimulation of glucose uptake by both stimuli in rat skeletal muscle.     

Characterization of the train-of-four response in fast and slow muscles: effect of d-tubocurarine, pancuronium, and vecuronium

The in vivo cat soleus and gastrocnemius muscles were used to compare isometric contraction strength and the train-of-four (T4) response (2 Hz for 2 s) of two muscle types (fast and slow) during onset of competitive neuromuscular blockade in order to determine the extent of the correlation between twitch depression and T4 fade. Prior to drug administration the muscles that were studied differed significantly in that the T4 ratio was 1.0 in the gastrocnemius and only 0.87 in the soleus. Three competitive neuromuscular-blocking agents were compared: d-tubocurarine, pancuronium, and vecuronium. d-Tubocurarine was found to produce a close correlation between the degrees of twitch strength depression and T4 for both muscles. However, these muscles demonstrated significantly different ED50 values (105 micrograms/kg for gastrocnemius, 150 micrograms/kg for soleus). Pancuronium also produced a similar relationship between twitch strength depression and T4 decrement for each muscle. In this case, however, there was little difference in their ED50 values for twitch depression (11.5 micrograms/kg for gastrocnemius, 13 micrograms/kg for soleus). The effects of vecuronium were quite different from the other two muscle relaxants. Although vecuronium produced a comparable correlation between twitch tension and T4 fade in fast muscle, no such relationship was found to exist in slow muscle. Even when the twitch strength was blocked to 18% of control, the soleus T4 response was depressed to only 75% of control. These results highlight major differences among competitive neuromuscular-blocking agents and suggest multiple sites of action.     

Protein synthesis and degradation in biopsies of rat skeletal muscle

The use of 20- to 40-mg biopsies of rat skeletal muscle to measure protein synthesis and degradation rates in vitro was investigated and compared to that of the intact extensor digitorum longus (EDL) and soleus muscles. During incubations in oxygenated Krebs-Ringer bicarbonate buffer with glucose, insulin, 23 amino acids at 10 times rat plasma levels, and [14C]tyrosine, the specific activity of intracellular tyrosine approximated that of the incubation medium and was constant in the biopsy, the EDL, and the soleus. The rate of incorporation of tyrosine into the protein of the biopsy was constant for 3 hr and was 39 and 32% of the rates of the EDL and soleus, respectively. The rate of release of tyrosine from protein in the biopsy during incubations in buffer with glucose and cycloheximide was constant for 3 hr and was intermediate between the rates of the EDL and soleus. The effects of starvation on the in vitro protein metabolism of the biopsy were the same as on the intact muscles. The 42% decrease in synthesis and the 53% increase in degradation in the biopsy were intermediate between the changes measured in the EDL and soleus muscles. The ability of this technique to identify proportional changes in the in vitro protein synthesis and degradation rates makes this a valid technique suitable for the measurement of changes of in vitro protein metabolism using serial biopsies from larger animals, including man.     

Enhancement of adult muscle regeneration by primary myoblast transplantation

Extensor digitorum longus muscles (EDL) of SCID mice were induced to undergo degeneration-regeneration subsequent to orthotopic, whole-muscle transplantation. Two days after transplantation some of these muscles received injections of primary myoblasts derived from EDL muscles of transgenic mice, which express nuclear localizing beta-galactosidase under the control of the myosin light-chain 3F promoter and enhancer. Nine weeks after transplantation, regenerated muscles that received exogenous myoblasts were compared to similarly transplanted muscles that received no further treatment and to unoperated EDL muscles in order to determine the effect of myoblast transfer on muscle regeneration. Many myofibers containing donor derived myonuclei could be identified in the regenerated muscles that had received exogenous myoblasts. The mass of the muscles subjected to transplantation only was significantly less (31% less) than that of unoperated muscles. The addition of exogenous myoblasts to the regenerating EDL resulted in a muscle mass similar to that of unoperated muscles. The absolute twitch and tetanic tensions and specific twitch and tetanic tensions of transplant-only muscles were 28%, 36%, 32%, and 41%, respectively, of those of unoperated muscles. Myoblast transfer increased the absolute twitch and tetanic tensions of the regenerated muscles by 65% and 74%, respectively, and their specific twitch and tetanic tensions were increased by 41% and 48%, respectively. These data suggest a possible role for the addition of exogenous, primary myoblasts in the treatment of traumatized and/or diseased muscles that are characterized by myofiber loss.     

The effects of enflurane,isoflurane, and intravenous anesthetics on rat diaphragmatic function and fatigability

We examined the effect of isoflurane, enflurane, midazolam, ketamine, propofol, and thiopental on diaphragmatic functions under unfatigued and fatigued conditions in 228 rat isolated muscle strips. Diaphragmatic twitch characteristics and tetanic contractions were measured before and after muscle fatigue, which was induced by repetitive tetanic contraction with or without exposure to one of the anesthetics at clinically relevant plasma concentrations, and at 10 and 100 times this concentration, or at 1, 2, and 3 minimum alveolar anesthetic concentration (MAC). Isoflurane, midazolam, ketamine, propofol, and thiopental did not induce a direct inotropic or lusitropic effect under unfatigued and fatigued conditions. Enflurane did not change contraction or relaxation in fresh isolated diaphragm, but enflurane at 2-3 MAC enhanced diaphragmatic fatigability itself and fatigue-induced impairment of twitch characteristics and tetanic tensions. These effects were greater at 3 MAC than at 2 MAC. Our findings suggest that the reduction of diaphragm function previously reported in in vivo experiments using propofol, midazolam, and isoflurane is not related to a direct effect on intrinsic diaphragmatic contractility. Our results also indicate that large concentrations of enflurane may impair the diaphragmatic function at sites other than excitation-contraction coupling. IMPLICATIONS: Enflurane did not change contraction or relaxation in fresh isolated rat diaphragm, but enhanced diaphragmatic fatigability itself and fatigue-induced impairment of twitch characteristics and tetanic tensions. Isoflurane, midazolam, ketamine, propofol, and thiopental had no direct effects on diaphragmatic functions under unfatigued and fatigued conditions. Isoflurane and these i.v. anesthetics may be advantageous over enflurane to anesthetize and/or sedate patients who are predisposed to diaphragmatic fatigue.     

Nitric oxide increases glucose uptake through a mechanism that is distinct from the insulin and contraction pathways in rat skeletal muscle

Insulin, contraction, and the nitric oxide (NO) donor, sodium nitroprusside (SNP), all increase glucose transport in skeletal muscle. Some reports suggest that NO is a critical mediator of insulin- and/or contraction-stimulated transport. To determine if the mechanism leading to NO-stimulated glucose uptake is similar to the insulin- or contraction-dependent signaling pathways, isolated soleus and extensor digitorum longus (EDL) muscles from rats were treated with various combinations of SNP (maximum 10 mmol/l), insulin (maximum 50 mU/ml), electrical stimulation to produce contractions (maximum 10 min), wortmannin (100 nmol/l), and/or the NO synthase (NOS) inhibitor NG-monomethyl-L-arginine (L-NMMA) (0.1 mmol/l). The combinations of SNP plus insulin and SNP plus contraction both had fully additive effects on 2-deoxyglucose uptake. Wortmannin completely inhibited insulin-stimulated glucose transport and only slightly inhibited SNP-stimulated 2-deoxyglucose uptake, whereas L-NMMA did not inhibit contraction-stimulated 2-deoxyglucose uptake. SNP significantly increased the activity of the alpha1 catalytic subunit of 5'AMP-activated protein kinase (AMPK), a signaling molecule that has been implicated in mediating glucose transport in fuel-depleted cells. Addition of the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (1 mg/ml) to the drinking water of rats for 2 days failed to affect the increase in muscle 2-deoxyglucose uptake in response to treadmill exercise. These data suggest that NO stimulates glucose uptake through a mechanism that is distinct from both the insulin and contraction signaling pathways.     

Akt2 is essential for the full effect of calorie restriction on insulin-stimulated glucose uptake in skeletal muscle

Brief calorie restriction (CR; 20 days of 60% of ad libitum [AL] intake) improves insulin-stimulated glucose transport, concomitant with enhanced phosphorylation of Akt2. The purpose of this study was to determine whether Akt2 is essential for the calorie restriction-induced enhancement in skeletal muscle insulin sensitivity. We measured insulin-stimulated 2-deoxyglucose (2DG) uptake in isolated extensor digitorum longus (EDL) and soleus muscles from male and female wild-type (WT) and Akt2-null (knockout [KO]) mice after ad libitum or calorie-restricted (20 days at 60% of AL) feeding. In WT mice, calorie restriction significantly enhanced insulin-stimulated 2DG uptake in both muscles regardless of sex. However, in KO mice, calorie restriction did not enhance insulin-stimulated 2DG in male or female EDL or in female soleus. Only in male KO soleus did calorie restriction significantly increase insulin-stimulated 2DG through an Akt2-independent mechanism, although 2DG uptake of the KO-CR group was reduced compared with the WT-CR soleus group. Akt2 serine phosphorylation was enhanced approximately two- to threefold in insulin-stimulated WT-CR versus WT-AL muscles. Calorie restriction induced an approximately 1.5- to 2-fold elevation in Akt1 phosphorylation of insulin-treated muscles, regardless of genotype, but this increase was insufficient to replace Akt2 for insulin-stimulated 2DG in Akt2-deficient muscles. These results indicate that Akt2 is essential for the full effect of brief calorie restriction on insulin-stimulated glucose uptake in skeletal muscle with physiologic insulin.     

Evidence that cathepsin B contributes to skeletal muscle protein breakdown during sepsis

The mechanisms of accelerated skeletal muscle protein degradation during sepsis have not been fully elucidated. Activity of the lysosomal protease cathepsin B is increased in skeletal muscle during various catabolic states other than sepsis. In the present study the protein degradation rate and cathepsin B activity were determined in extensor digitorum longus and soleus muscles from nonseptic and septic rats. The protein degradation rate during incubation in vitro with or without the cathepsin B inhibitor leupeptin was also determined. Both protein degradation and cathepsin B activity were increased in muscles from septic rats. Incubation with leupeptin reduced, but did not normalize, the protein degradation rate in both extensor digitorum longus and soleus muscles from septic animals. These studies suggest that increased cathepsin B activity contributes to the accelerated muscle proteolysis seen during sepsis and that proteases other than cathepsin B are also involved.     

Ischemia Increases the Twitch Latent Period in the Soleus and Extensor Carpi Radialis Longus Muscles from Adult Rats

Complete ischemia and reperfusion effects on twitch force (∫(F·t)), twitch latent period (TLP), maximal rate of rise of twitch tension (δF/δt)_max, and twitch maximum relaxation rate (TMRR) were assessed. We divided 36 adult rats into four groups; two control groups (n = 9), a group undergoing 1 hour of ischemia followed by 1 hour of reperfusion (n = 9), and one group exposed to 2 hours of ischemia followed by 1 hour of reperfusion (n = 9). We have induced twitch contractions every 10 minutes in the soleus and the extensor carpi radialis longus (ECRL). Twitch contractions were recorded and then analyzed for ∫(F·t), TLP, (δF/δt)_max, and TMRR. During 1 hour and 40 minutes of ischemia, TLP increased to 179 ± 24% (p < 0.05) in the soleus and to 184 ± 16% (p < 0.05) in the ECRL, an effect that was partially recovered during 1 hour of reperfusion. This increase started after 20 minutes of ischemia in the soleus and after 40 minutes of ischemia in the ECRL. The increase was faster in the ECRL and peaked at the same time for both muscular groups. ∫(F·t) and (δF/δt)_max decreased during 1 hour of ischemia to 46 ± 7% (p < 0.05) in the soleus and to 40 ± 7% (p < 0.05) in the ECRL. TMRR decreased during 1 hour of ischemia to 39 ± 5% (p < 0.05) in the soleus and to 54 ± 8% (p < 0.05) in the ECRL. During 1 hour of reperfusion all of them recovered close to control values.     

Glucose utilization rates and insulin sensitivity in vivo in tissues of virgin and pregnant rats

In vivo studies have shown that insulin resistance in late pregnancy results from a decreased sensitivity of liver and peripheral tissues. In the present study, measurements of the rates of glucose utilization by skeletal muscles (soleus, extensor digitorum longus, epitrochlearis, and diaphragm), white adipose tissue, and brain of virgin and 19-day pregnant rats were performed in the basal condition and during a euglycemic, hyperinsulinemic (400 microU/ml) clamp to quantify the partition of glucose utilization and to identify the tissues other than liver responsible for insulin resistance. Fetal and placental glucose utilization rates were also measured in pregnant rats. The fetal glucose utilization rate (22 mg/min/kg) was very high and was not stimulated by physiologic maternal hyperinsulinemia. By contrast, the placental glucose utilization rate (29 mg/min/kg) was increased by 30% during hyperinsulinemia. The glucose utilization rate of the conceptus represented 23% of the maternal glucose utilization rate in the basal state. Glucose utilization rates in the basal condition were not statistically altered by pregnancy in brain, skeletal muscles, and white adipose tissue. During hyperinsulinemia (400 microU/ml), glucose utilization rates in extensor digitorum longus, epitrochlearis, and white adipose tissue were 30-70% lower in pregnant than in virgin rats. Insulin sensitivity of glucose metabolism in all the tissues tested other than brain was 50% lower in pregnant than in virgin rats. We conclude that skeletal muscles and, to a smaller extent, adipose tissue are involved in the insulin resistance of late pregnancy.     

Experimental study on the influence of tension, immobilisation and denervation on muscle transplantation

To observe the effects of tension and immobilisation on denervated muscle, rats' denervated soleus muscles were transplanted orthotopically at different tensions: high, neutral, moderate and low tension with immobilisation. Results were evaluated by measuring muscle mass, twitch and tetanic tension, and histologically by HE staining. The results showed better preservation of muscle weight in the high tension group. Atrophy and loss of function were rapid during the first 4 weeks and were greatest in the low tension group. Rate of atrophy was slowed and relatively stabilised at the eighth postoperative week. We conclude that increased tension with immobilisation produced slower initial atrophy and loss of function in denervated muscle flaps. Although slower, the atrophy continued during the prolonged immobilisation and there was no significant difference compared with neutral tension at a later period. Moreover, immobilisation produced atrophy and affected function regardless of the amount of tension. Increased tension decelerates and decreased tension accelerates denervation atrophy of muscle. Thus denervation, immobilisation and reduced tension are all detrimental in muscle transplantation.