beta-Alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinters.

Carnosine (beta-alanyl-l-histidine) is present in high concentrations in human skeletal muscle. The ingestion of beta-alanine, the rate-limiting precursor of carnosine, has been shown to elevate the muscle carnosine content. We aimed to investigate, using proton magnetic resonance spectroscopy (proton MRS), whether oral supplementation with beta-alanine during 4 wk would elevate the calf muscle carnosine content and affect exercise performance in 400-m sprint-trained competitive athletes. Fifteen male athletes participated in a placebo-controlled, double-blind study and were supplemented orally for 4 wk with either 4.8 g/day beta-alanine or placebo. Muscle carnosine concentration was quantified in soleus and gastrocnemius by proton MRS. Performance was evaluated by isokinetic testing during five bouts of 30 maximal voluntary knee extensions, by endurance during isometric contraction at 45% maximal voluntary contraction, and by the indoor 400-m running time. beta-Alanine supplementation significantly increased the carnosine content in both the soleus (+47%) and gastrocnemius (+37%). In placebo, carnosine remained stable in soleus, while a small and significant increase of +16% occurred in gastrocnemius. Dynamic knee extension torque during the fourth and fifth bout was significantly improved with beta-alanine but not with placebo. Isometric endurance and 400-m race time were not affected by treatment. In conclusion, 1) proton MRS can be used to noninvasively quantify human muscle carnosine content; 2) muscle carnosine is increased by oral beta-alanine supplementation in sprint-trained athletes; 3) carnosine loading slightly but significantly attenuated fatigue in repeated bouts of exhaustive dynamic contractions; and 4) the increase in muscle carnosine did not improve isometric endurance or 400-m race time.     

Carnosine and anserine in working muscles--study using proton NMR spectroscopy]

NMR spectroscopy was used to study carnosine and anserine metabolism in rat tissues under intensive muscle loading. Muscle loading was accompanied by the dipeptide (predominantly anserine) accumulation in muscle tissues. Preliminary per os administration of carnosine (250 mg/kg of body mass) did not increase the dipeptide content in muscle tissues but diminished the lactate content in rat muscles under intensive muscle loading.     

Reduced muscle carnosine content in type 2, but not in type 1 diabetic patients

Carnosine is present in high concentrations in skeletal muscle where it contributes to acid buffering and functions also as a natural protector against oxidative and carbonyl stress. Animal studies have shown an anti-diabetic effect of carnosine supplementation. High carnosinase activity, the carnosine degrading enzyme in serum, is a risk factor for diabetic complications in humans. The aim of the present study was to compare the muscle carnosine concentration in diabetic subjects to the level in non-diabetics. Type 1 and 2 diabetic patients and matched healthy controls (total n=58) were included in the study. Muscle carnosine content was evaluated by proton magnetic resonance spectroscopy (3 Tesla) in soleus and gastrocnemius. Significantly lower carnosine content (-45%) in gastrocnemius muscle, but not in soleus, was shown in type 2 diabetic patients compared with controls. No differences were observed in type 1 diabetic patients. Type II diabetic patients display a reduced muscular carnosine content. A reduction in muscle carnosine concentration may be partially associated with defective mechanisms against oxidative, glycative and carbonyl stress in muscle.     

Vegetarianism,female gender and increasing age,but not <Emphasis Type="Italic">CNDP1</Emphasis> genotype,are associated with reduced muscle carnosine levels in humans

Carnosine is found in high concentrations in skeletal muscles, where it is involved in several physiological functions. The muscle carnosine content measured within a population can vary by a factor 4. The aim of this study was to further characterize suggested determinants of the muscle carnosine content (diet, gender and age) and to identify new determinants (plasma carnosinase activity and testosterone). We investigated a group of 149 healthy subjects, which consisted of 94 men (12 vegetarians) and 55 women. Muscle carnosine was quantified in M. soleus, gastrocnemius and tibialis anterior using magnetic resonance proton spectroscopy and blood samples were collected to determine CNDP1 genotype, plasma carnosinase activity and testosterone concentrations. Compared to women, men have 36, 28 and 82% higher carnosine concentrations in M. soleus, gastrocnemius and tibialis anterior muscle, respectively, whereas circulating testosterone concentrations were unrelated to muscle carnosine levels in healthy men. The carnosine content of the M. soleus is negatively related to the subjects’ age. Vegetarians have a lower carnosine content of 26% in gastrocnemius compared to omnivores. In contrast, there is no difference in muscle carnosine content between omnivores with a high or low ingestion of β-alanine. Muscle carnosine levels are not related to the polymorphism of the CNDP1 gene or to the enzymatic activity of the plasma carnosinase. In conclusion, neither CNDP1 genotype nor the normal variation in circulating testosterone levels affects the muscular carnosine content, whereas vegetarianism, female gender and increasing age are the factors associated with reduced muscle carnosine stores.     

Gender-related differences in carnosine,anserine and lysine content of murine skeletal muscle

Summary. The aminoacyl-imidazole dipeptides carnosine (-alanyl-L-histidine) and anserine (-alanyl-1-methyl-histidine) are present in relatively high concentrations in excitable tissues, such as muscle and nervous tissue. In the present study we describe the existence of a marked sexual dimorphism of carnosine and anserine in skeletal muscles of CD1 mice. In adult animals the concentrations of anserine were higher than those of carnosine in all skeletal muscles studied, and the content of aminoacyl-imidazole dipeptides was remarkably higher in males than in females. Postnatal ontogenic studies and hormonal manipulations indicated that carnosine synthesis was up-regulated by testosterone whereas anserine synthesis increased with age. Regional variations in the concentrations of the dipeptides were observed in both sexes, skeletal muscles from hind legs having higher amounts of carnosine and anserine than those present in fore legs or in the pectoral region. The concentration of L-lysine in skeletal muscles also showed regional variations and a sexual dimorphic pattern with females having higher levels than males in all muscles studied. The results suggest that these differences may be related with the anabolic action of androgens on skeletal muscle.     

The influence of sex, age and heritability on human skeletal muscle carnosine content

The dipeptide carnosine is found in high concentrations in human skeletal muscle and shows large inter-individual differences. Sex and age are determining factors, however, systematic studies investigating the sex effects on muscle carnosine content throughout the human lifespan are lacking. Despite the large inter-individual variation, the intra-individual variation is limited. The question may be asked whether the carnosine content is a muscle characteristic which may be largely genetically determined. A total of 263 healthy male and female subjects of 9-83 years were divided into five different age groups: prepubertal children (PC), adolescents (A), young adults (YA), middle adults (MA) and elderly (E). We included 25 monozygotic and 22 dizygotic twin pairs among the entire study population to study the heritability. The carnosine content was measured non-invasively in the gastrocnemius medialis and soleus by proton magnetic resonance spectroscopy (1H-MRS). In boys, carnosine content was significantly higher (gastrocnemius 22.9%; soleus 44.6%) in A compared to PC, while it did not differ in girls. A decrease (~16%) was observed both in males and females from YA to MA. However, elderly did not have lower carnosine levels in comparison with MA. Higher correlations were found in monozygotic (r=0.86) compared to dizygotic (r=0.51) twins, in soleus muscle, but not in gastrocnemius. In conclusion, this study found an effect of puberty on muscle carnosine content in males, but not in females. Muscle carnosine decreased mainly during early adulthood and hardly from adulthood to elderly. High intra-twin correlations were observed, but muscle-dependent differences preclude clear conclusions toward heritability.     

The carnosine content of vastus lateralis is elevated in resistance-trained bodybuilders

Resistance training is associated with periods of acute intracellular hypoxia with increased H(+) production and low intramuscular pH. The aim of this study was to investigate the possible adaptive response in muscle carnosine (beta-alanyl-L-histidine) in bodybuilders. Extracts of biopsies of m. vastus lateralis of 6 national-level competitive bodybuilders and 6 age-matched untrained but moderately active healthy subjects were analyzed by high-performance liquid chromatography. Significant differences were shown in carnosine (p < 0.001) and histidine (p < 0.05). Muscle carnosine in bodybuilders was twice that in controls. The carnosine contents measured are the highest recorded in human muscle and represent a 20% contribution to muscle buffering capacity. Taurine was 38% lower in bodybuilders, though the difference was not significant. Possible causes for the changes observed are prolonged repetitive exposure to low muscle pH, change of diet or dietary supplement use, or the use of anabolic steroids. The increase in buffering capacity could influence the ability to carry out intense muscular activity.     

Adaptive strength gains in dystrophic muscle exposed to repeated bouts of eccentric contraction

The objective of this study was to determine the functional recovery and adaptation of dystrophic muscle to multiple bouts of contraction-induced injury. Because lengthening (i.e., eccentric) contractions are extremely injurious for dystrophic muscle, it was considered that repeated bouts of such contractions would exacerbate the disease phenotype in mdx mice. Anterior crural muscles (tibialis anterior and extensor digitorum longus) and posterior crural muscles (gastrocnemius, soleus, and plantaris) from mdx mice performed one or five repeated bouts of 100 electrically stimulated eccentric contractions in vivo, and each bout was separated by 10-18 days. Functional recovery from one bout was achieved 7 days after injury, which was in contrast to a group of wild-type mice, which still showed a 25% decrement in electrically stimulated isometric torque at that time point. Across bouts there was no difference in the immediate loss of strength after repeated bouts of eccentric contractions for mdx mice (-70%, P = 0.68). However, after recovery from each bout, dystrophic muscle had greater torque-generating capacity such that isometric torque was increased ～38% for both anterior and posterior crural muscles at bout 5 compared with bout 1 (P < 0.001). Moreover, isolated extensor digitorum longus muscles excised from in vivo-tested hindlimbs 14-18 days after bout 5 had greater specific force than contralateral control muscles (12.2 vs. 10.4 N/cm(2), P = 0.005) and a 20% greater maximal relaxation rate (P = 0.049). Additional adaptations due to the multiple bouts of eccentric contractions included rapid recovery and/or sparing of contractile proteins, enhanced parvalbumin expression, and a decrease in fiber size variability. In conclusion, eccentric contractions are injurious to dystrophic skeletal muscle; however, the muscle recovers function rapidly and adapts to repeated bouts of eccentric contractions by improving strength.     

Changes in the mechanical properties of human and amphibian muscle after eccentric exercise

Following a series of eccentric contractions, that is stretching of the muscle while generating active tension, the length-tension relationship of isolated amphibian muscle has been shown to shift towards longer muscle lengths (Katz 1939; Wood et al. 1993). Here we report observations of electrically stimulated ankle extensor muscles of nine human subjects, demonstrating a similar shift in optimum angle for torque generation [3.9 (1.5)°] following exercise on an inclined treadmill that involved eccentric contractions in one leg. (All values are means with the SEMs in parentheses.) The shift in the unexercised, control leg was significantly less [mean 0.4 (0.7)°P < 0.05]. Correlated with this shift was a drop in torque [25.1 (5.6)% for the experimental leg; 1.6 (0.7)% for the control leg, P < 0.002]. Optimum angles returned to pre-exercise values by 2 days post-exercise, while torque took a week to recover. A similar shift in optimum length [12 (1.3)% of rest length] was obtained for five toad (Bufo marinus) sartorius muscles subjected to 25 eccentric contractions. Isometrically contracted control muscles showed a smaller shift [3.5 (1.6)%, n = 5]. Accompanying the shift was a drop in tension of 46 (3)% after the eccentric contractions [control isometric, 23 (6)%, P < 0.0001]. By 5 h after the eccentric contractions the shift had returned to control values, while tension had not recovered. When viewed with an electron microscope, sartorius muscles fixed immediately after the eccentric contractions exhibited many small, and a few larger, regions of myofilament disruption. In muscles fixed 5 h after the contractions, no small regions of disruption were visible, and the number of large regions was no greater than in those muscles fixed immediately after the eccentric contractions. These disruptions are interpreted as the cause of the shift in length-tension relationship. Accepted: 9 January 1997     

Beta-alanine (Carnosyn?) supplementation in elderly subjects (60–80?years): effects on muscle carnosine content and physical capacity

The aim of this study was to investigate the effects of beta-alanine supplementation on exercise capacity and the muscle carnosine content in elderly subjects. Eighteen healthy elderly subjects (60-80 years, 10 female and 4 male) were randomly assigned to receive either beta-alanine (BA, n=12) or placebo (PL, n=6) for 12 weeks. The BA group received 3.2 g of beta-alanine per day (2×800 mg sustained-release Carnosyn? tablets, given 2 times per day). The PL group received 2× (2×800 mg) of a matched placebo. At baseline (PRE) and after 12 weeks (POST-12) of supplementation, assessments were made of the muscle carnosine content, anaerobic exercise capacity, muscle function, quality of life, physical activity and food intake. A significant increase in the muscle carnosine content of the gastrocnemius muscle was shown in the BA group (+85.4%) when compared with the PL group (+7.2%) (p=0.004; ES: 1.21). The time-to-exhaustion in the constant-load submaximal test (i.e., TLIM) was significantly improved (p=0.05; ES: 1.71) in the BA group (+36.5%) versus the PL group (+8.6%). Similarly, time-to-exhaustion in the incremental test was also significantly increased (p=0.04; ES 1.03) following beta-alanine supplementation (+12.2%) when compared with placebo (+0.1%). Significant positive correlations were also shown between the relative change in the muscle carnosine content and the relative change in the time-to-exhaustion in the TLIM test (r=0.62; p=0.01) and in the incremental test (r=0.48; p=0.02). In summary, the current data indicate for the first time, that beta-alanine supplementation is effective in increasing the muscle carnosine content in healthy elderly subjects, with subsequent improvement in their exercise capacity.     

Effect of two β-alanine dosing protocols on muscle carnosine synthesis and washout

Carnosine (β-alanyl-L-histidine) is found in high concentrations in skeletal muscle and chronic β-alanine (BA) supplementation can increase carnosine content. This placebo-controlled, double-blind study compared two different 8-week BA dosing regimens on the time course of muscle carnosine loading and 8-week washout, leading to a BA dose-response study with serial muscle carnosine assessments throughout. Thirty-one young males were randomized into three BA dosing groups: (1) high-low: 3.2 g BA/day for 4 weeks, followed by 1.6 g BA/day for 4 weeks; (2) low-low: 1.6 g BA/day for 8 weeks; and (3) placebo. Muscle carnosine in tibialis-anterior (TA) and gastrocnemius (GA) muscles was measured by 1H-MRS at weeks 0, 2, 4, 8, 12 and 16. Flushing symptoms and blood clinical chemistry were trivial in all three groups and there were no muscle carnosine changes in the placebo group. During the first 4 weeks, the increase for high-low (TA 2.04 mmol/kgww, GA 1.75 mmol/kgww) was ~twofold greater than low-low (TA 1.12 mmol/kgww, GA 0.80 mmol/kgww). 1.6 g BA/day significantly increased muscle carnosine within 2 weeks and induced continual rises in already augmented muscle carnosine stores (week 4-8, high-low regime). The dose-response showed a carnosine increase of 2.01 mmol/kgww per 100 g of consumed BA, which was only dependent upon the total accumulated BA consumed (within a daily intake range of 1.6-3.2 g BA/day). Washout rates were gradual (0.18 mmol/kgww and 0.43 mmol/kgww/week; ~2%/week). In summary, the absolute increase in muscle carnosine is only dependent upon the total BA consumed and is not dependent upon baseline muscle carnosine, the muscle type, or the daily amount of supplemented BA.     

Force depression following muscle shortening in sub-maximal voluntary contractions of human adductor pollicis

Mechanical properties of skeletal muscles are often studied for controlled, electrically induced, maximal, or supra-maximal contractions. However, many mechanical properties, such as the force-length relationship and force enhancement following active muscle stretching, are quite different for maximal and sub-maximal, or electrically induced and voluntary contractions. Force depression, the loss of force observed following active muscle shortening, has been observed and is well documented for electrically induced and maximal voluntary contractions. Since sub-maximal voluntary contractions are arguably the most important for everyday movement analysis and for biomechanical models of skeletal muscle function, it is important to study force depression properties under these conditions. Therefore, the purpose of this study was to examine force depression following sub-maximal, voluntary contractions. Sets of isometric reference and isometric-shortening-isometric test contractions at 30% of maximal voluntary effort were performed with the adductor pollicis muscle. All reference and test contractions were executed by controlling force or activation using a feedback system. Test contractions included adductor pollicis shortening over 10 degrees, 20 degrees, and 30 degrees of thumb adduction. Force depression was assessed by comparing the steady-state isometric forces (activation control) or average electromyograms (EMGs) (force control) following active muscle shortening with those obtained in the corresponding isometric reference contractions. Force was decreased by 20% and average EMG was increased by 18% in the shortening test contractions compared to the isometric reference contractions. Furthermore, force depression was increased with increasing shortening amplitudes, and the relative magnitudes of force depression were similar to those found in electrically stimulated and maximal contractions. We conclude from these results that force depression occurs in sub-maximal voluntary contractions, and that force depression may play a role in the mechanics of everyday movements, and therefore may have to be considered in biomechanical models of human movement.     

Effect of neurogenic inactivity on posttetanic responses of rat fast muscle

At a short-term tetanic stimulation of fast muscle in response to subsequent single stimulation there is recorded a temporary increase of the strength of single contractions that returns to the initial background after 6–10 min. This phenomenon is called posttetanic potentiation (PTP) and is recorded only in fast muscles. The goal of the present work was a study of effect of motor innervation on the course of PTP in rat m. extensor digitorum longus (m. Edl). It has been established that the first signs of effect of motor denervation on the PTP course after section of sciatic nerve in the area of popliteal fossa are recorded as early as at the 4th day after denervation and are expressed in a decrease of strength of single contractions after cessation of tetanic stimulation. These changes reach its maximum at the 14–15th day after denervation when effect of PTP in denervated muscle does not appear at all. Pharmacological analysis of the studied phenomenon has shown that dantrolen (10 μM) suppresses amplitude of the single contraction, but does not prevent the appearance of PTP in intact muscle. In the denervated m. Edl, instead of the appearance of PTP, after a brief slight increase, a gradual decrease of the strength of contraction is recorded. Thus, it can be concluded that no significant PTP changes are present under action of dantrolen. It has been established that after the 10-min muscle incubation in Ringer’s solution with caffeine (4 mM), strength of the single contraction in intact and denervated muscles increases by approximately equal value. Tetanization of intact muscle increases strength of the single contraction approximately by 7% more than this occurs after incubation with caffeine, i.e., this substance reduces the capability of muscle for the appearance of PTP. On denervated muscle, caffeine increases strength of singly contraction, but does not potentiate development of PTP. The obtained data allow concluding about the existence of different mechanisms underlying the pretetatnic contraction and posttetanic potentiation of the single contraction. The main difference between two types of contractions can be recruiting of additional DICR-channels in the process of contraction under conditions of PTP.     

Effect of long-term arterial hypotension on the relative volume of functioning capillaries in working skeletal muscles

In control rats, the relative red cell volume, mirroring the number of the functioning capillaries, was substantially greater in the soleus than in the gastrocnemius muscle, while the rise of this parameter seen during contraction of both the muscles, provoked by stimulation of the sciatic nerve, amounted to 37 and 54%, respectively. Fourteen days and 3-4 months after abdominal aorta constriction by a metal spiral, that produced a 30-50% lowering of the blood pressure in the vessels of the animal's body posterior, contractions of the gastrocnemius muscle did not provoke any increase in the relative red cell volume, whereas contractions of the soleus muscle were accompanied by a marked elevation of the relative red cell volume. It is assumed that the mechanisms underlying the working hyperemia of the gastrocnemius and soleus muscles are different.     

Effects of blood pressure on force production in cat and human muscle

In anesthetized cats reducing local arterial pressure from 125 to 75 Torr decreased blood flow (53 +/- 5%) and force production (57 +/- 7%) in soleus and medial gastrocnemius. Force was produced in these muscles by aerobic, slowly fatiguing fibers. Similar reductions in arterial pressure did not affect force production in caudofemoralis, which contains mainly fast-fatiguing fibers. In human subjects the electromyogram produced by the ankle extensors during rhythmic constant-force contractions increased as the contracting muscles were raised above the heart during legs-up tilt. This suggests that force production of active muscle fibers at a given level of activation fell with muscle perfusion pressure, thus requiring augmentation of muscle activity to sustain the standard contractions. Because aerobic fibers contributed to these contractions, it appears that force production of human muscle fibers is sensitive to small changes in perfusion pressure and, presumably, blood flow. The critical dependence of developed muscular force on blood pressure is of importance to motor control and may also play a significant role in cardiovascular control during exercise.     

The pressor response to voluntary and electrically evoked isometric contractions in man

Blood pressure and heart rate changes during sustained isometric exercise were studied in 11 healthy male volunteers. The responses were measured during voluntary and involuntary contractions of the biceps brachii at 30% of maximal voluntary contraction (MVC), and the triceps surae at 30% and 50% MVC. Involuntary contractions were evoked by percutaneous electrical stimulation of the muscle. Measurements of the time to peak tension of maximal twitch showed the biceps brachii (67.0 +/- 7.9 ms) muscle to be rapidly contracting, and the triceps surae (118.0 +/- 10.5 ms) to be slow contracting. The systolic and diastolic blood pressures increased linearly throughout the contractions, and systolic blood pressure increased more rapidly than diastolic. There was no significant difference in response to stimulated or voluntary contractions, nor was there any significant difference between the responses to contractions of the calf or arm muscles at the same relative tension. In contrast the heart rate rose to a higher level (P less than 0.01) in the biceps brachii than the triceps surae at given % MVC, and during voluntary compared with the electrically evoked contractions in the two muscle groups. It was concluded that the arterial blood pressure response to isometric contractions, unlike heart rate, is primarily due to a reflex arising within the active muscles (cf. Hultman and Sj?holm 1982) which is associated with relative tension but independent of contraction time and muscle mass.     

Medial gastrocnemius muscle fascicle active torque-length and Achilles tendon properties in young adults with spastic cerebral palsy

Individuals with spastic cerebral palsy (CP) typically experience muscle weakness. The mechanisms responsible for muscle weakness in spastic CP are complex and may be influenced by the intrinsic mechanical properties of the muscle and tendon. The purpose of this study was to investigate the medial gastrocnemius (MG) muscle fascicle active torque-length and Achilles tendon properties in young adults with spastic CP. Nine relatively high functioning young adults with spastic CP (GMFCS I, 17±2 years) and 10 typically developing individuals (18±2 years) participated in the study. Active MG torque-length and Achilles tendon properties were assessed under controlled conditions on a dynamometer. EMG was recorded from leg muscles and ultrasound was used to measure MG fascicle length and Achilles tendon length during maximal isometric contractions at five ankle angles throughout the available range of motion and during passive rotations imposed by the dynamometer. Compared to the typically developing group, the spastic CP group had 33% lower active ankle plantarflexion torque across the available range of ankle joint motion, partially explained by 37% smaller MG muscle and 4% greater antagonistic co-contraction. The Achilles tendon slack length was also 10% longer in the spastic CP group. This study confirms young adults with mild spastic CP have altered muscle–tendon mechanical properties. The adaptation of a longer Achilles tendon may facilitate a greater storage and recovery of elastic energy and partially compensate for decreased force and work production by the small muscles of the triceps surae during activities such as locomotion.     

Muscle activation in the contralateral passive shoulder during isometric shoulder abduction in patients with unilateral shoulder pain.

Studies have shown an increased muscle activation at the opposite passive side during unilateral contractions. The purpose of the present study was to examine the influence of pain on muscle activation in the passive shoulder during unilateral shoulder abduction. Ten patients with unilateral rotator tendinosis of the shoulder and nine healthy controls performed unilateral maximal voluntary contractions (MVC) and sustained submaximal contractions with and without subacromial injections of local anaesthetics of the afflicted shoulder. Muscle activation was recorded by electromyography (EMG) from the trapezius, deltoid, infraspinatus and supraspinatus muscles in both shoulders. During MVCs, the EMG amplitude from muscles of the passive afflicted side was not different in patients and controls, and was not influenced by pain alterations. In contrast, the EMG amplitude from the muscles of the passive unafflicted side was lower in the patients and increased after pain reduction. During the sustained submaximal contraction the EMG amplitude increased gradually in the passive shoulder to 15-30% of the EMG amplitude observed during MVC. This response was not influenced by differences in pain. We conclude that muscle activation of the passive shoulder was closely related to the activation of the contracting muscles and thus related to central motor drive, and not directly influenced by changes in pain.     

Length dependence of active force production in skeletal muscle.

The sliding filament and cross-bridge theories of muscle contraction provide discrete predictions of the tetanic force-length relationship of skeletal muscle that have been tested experimentally. The active force generated by a maximally activated single fiber (with sarcomere length control) is maximal when the filament overlap is optimized and is proportionally decreased when overlap is diminished. The force-length relationship is a static property of skeletal muscle and, therefore, it does not predict the consequences of dynamic contractions. Changes in sarcomere length during muscle contraction result in modulation of the active force that is not necessarily predicted by the cross-bridge theory. The results of in vivo studies of the force-length relationship suggest that muscles that operate on the ascending limb of the force-length relationship typically function in stretch-shortening cycle contractions, and muscles that operate on the descending limb typically function in shorten-stretch cycle contractions. The joint moments produced by a muscle depend on the moment arm and the sarcomere length of the muscle. Moment arm magnitude also affects the excursion (length change) of a muscle for a given change in joint angle, and the number of sarcomeres arranged in series within a muscle fiber determines the sarcomere length change associated with a given excursion.     

Muscle Histidine-Containing Dipeptides Are Elevated by Glucose Intolerance in Both Rodents and Men

Objective

Muscle carnosine and its methylated form anserine are histidine-containing dipeptides. Both dipeptides have the ability to quench reactive carbonyl species and previous studies have shown that endogenous tissue levels are decreased in chronic diseases, such as diabetes.

Design and Methods

Rodent study: Skeletal muscles of rats and mice were collected from 4 different diet-intervention studies, aiming to induce various degrees of glucose intolerance: 45% high-fat feeding (male rats), 60% high-fat feeding (male rats), cafeteria feeding (male rats), 70% high-fat feeding (female mice). Body weight, glucose-tolerance and muscle histidine-containing dipeptides were assessed. Human study: Muscle biopsies were taken from m. vastus lateralis in 35 males (9 lean, 8 obese, 9 prediabetic and 9 newly diagnosed type 2 diabetic patients) and muscle carnosine and gene expression of muscle fiber type markers were measured.

Results

Diet interventions in rodents (cafeteria and 70% high-fat feeding) induced increases in body weight, glucose intolerance and levels of histidine-containing dipeptides in muscle. In humans, obese, prediabetic and diabetic men had increased muscle carnosine content compared to the lean (+21% (p>0.1), +30% (p<0.05) and +39% (p<0.05), respectively). The gene expression of fast-oxidative type 2A myosin heavy chain was increased in the prediabetic (1.8-fold, p<0.05) and tended to increase in the diabetic men (1.6-fold, p = 0.07), compared to healthy lean subjects.

Conclusion

Muscle histidine-containing dipeptides increases with progressive glucose intolerance, in male individuals (cross-sectional). In addition, high-fat diet-induced glucose intolerance was associated with increased muscle histidine-containing dipeptides in female mice (interventional). Increased muscle carnosine content might reflect fiber type composition and/or act as a compensatory mechanism aimed at preventing cell damage in states of impaired glucose tolerance.