Muscle Biochemistry Research Articles

Impact of Endurance Exercise Training in the Fasted State on Muscle Biochemistry and Metabolism in Healthy Subjects: Can These Effects be of Particular Clinical Benefit to Type2 Diabetes Mellitus and Insulin-Resistant Patients?

Exercise trainingintervention is a cornerstone in the care of type2 diabetes mellitus (T2DM) and insulin resistance (IR), and it is pursued in order to optimize exercise interventions for these patients. In this regard, the nutritional state of patients during exercise (being in the fed or fasted state) can be of particular interest. The aim of the present review is to describe the impact of endurance exercise (training) in the fasted versus fed state on parameters of muscle biochemistry and metabolism linked to glycemic control or insulin sensitivity in healthy subjects. From these data it can then be deduced whether exercise training in the fasted state may be relevant to patients with T2DM or IR. In healthy subjects, acute endurance exercise in the fasted state is accompanied by lower blood insulin and elevated blood free fatty acid concentrations, stable blood glucose concentrations (in the first 60-90min), superior intramyocellular triacylglycerol oxidation and whole-body lipolysis, and muscle glycogen preservation. Long-term exercise training in the fasted state in healthy subjects is associated with greater improvements in insulin sensitivity, basal muscle fat uptake capacity, and oxidation. Therefore, promising results of exercise (training) in the fasted state have been found in healthy subjects on parameters of muscle biochemistry and metabolism linked to insulin sensitivity and glycemic control. Whether exercise training intervention in which exercise sessions are organized in the fasted state may be more effective in improving insulin sensitivity or glycemic control in T2DM patients and insulin-resistant individuals warrants investigation.

482. Local and Systemic Gene Editing in a Mouse Model of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a highly prevalent genetic disorder leading to muscle wasting, loss of ambulation, and premature death by the third decade of life. DMD is caused by gene deletions, duplications, or nonsense mutations leading to the loss of dystrophin, an essential musculoskeletal protein. Gene therapy has held tremendous promise for the treatment of monogenic disorders, yet an effective gene replacement therapy has been elusive. Genome editing has been established as a potential approach to correct the dystrophin gene in cultured human cells by excising non-essential exons from the dystrophin gene producing a shortened yet in-frame dystrophin protein (1). In contrast to gene replacement therapy, genome editing repairs the causative mutation in the native genomic context with the potential for permanent gene repair. Recently, we and others have demonstrated that CRISPR/Cas9 genome editing in neonatal and adult mouse models of DMD restores dystrophin expression, improves muscle biochemistry, and strengthens muscle force generation (2-4). However, further optimization of the approach for systemic gene correction is still needed.To target the dystrophin gene in the mdx mouse, the 3.2kb S. aureus Cas9 and two guide RNAs (gRNA) targeting intronic regions surrounding exon 23 were packaged into an adeno-associated virus (AAV). Double stranded breaks created by Cas9 were repaired with the relatively efficient non-homologous end joining pathway leading to excision of the nonsense mutation in exon 23. AAV vectors were injected intramuscularly into the tibialis anterior muscle in adult mice and intravenously into neonatal mice and adult mice and characterized for gene deletions, dystrophin restoration, and improvements in muscle physiology.Local correction restored overall dystrophin levels to 8% by western blot with 67% of muscle fibers positive for dystrophin by immunofluorescence. Repeated cycles of eccentric contraction showed 60% resistance to damage compared to sham-treated mice. Systemic correction was achieved through IP injection into P2 neonates with dystrophin restoration primarily in the cardiac muscle and skeletal muscle surrounding the peritoneal cavity. IV administration in adult mice restored dystrophin expression in the cardiac muscle. Improved systemic distribution and correction was achieved with intravenous administration into P2 neonates with AAV8 or AAV9 (Fig. 1Fig. 1).Figure 1Intravenously administered AAV restores dystrophin in cardiac and skeletal muscle in P2 neonates after 8 weeks of treatement. a) Cardiac muscle. b) Tibialis anterior muscle. Scale bar = 200µm, green - dystrophin, blue - DAPI.View Large Image | Download PowerPoint SlideThis study establishes CRISPR/Cas9-based gene editing as a promising approach for the treatment of DMD. Ongoing work to improve the efficiency and safety of in vivo gene editing includes the incorporation of muscle specific promoters, minimization of vector packaging, and optimization of AAV serotype.1. Ousterout et al. Nat Comm 2015. | 2. Nelson et al. Science 2015 | 3. Tabebordbar et al. Science 2015 | 4. Long et al. Science 2015

Arnold M. Katz, MD

Arnold M. Katz was born in Chicago. His mother was a piano teacher; his father, Louis N. Katz, was an internationally renowned cardiologist and cardiovascular physiologist who received a Lasker award and was President of both the American Physiological Society and the American Heart Association. As an undergraduate at the University of Chicago, Arnold spent a summer at the Marine Biological Laboratory in Woods Hole, Massachusetts, where he participated in a study of the physico-chemical properties of skeletal muscle. As a medical student, he spent 2 summers in his father’s laboratory at Michael Reese Hospital in Chicago studying control of and interactions between coronary blood flow, left ventricular volume, and the energetics of the heart. In 1955, he first authored his first paper in Circulation Research on this subject.1 Thus, even before completing medical school, he had already worked in 2 areas—muscle chemistry and control of ventricular performance—to which he devoted much of his life as an investigator. After receiving his MD cum laude from Harvard Medical School in 1956, Katz trained in internal medicine at the Massachusetts General Hospital. He spent 2 years in the Laboratory of Nobel Prize–winning biochemist Christian B. Anfinsen Jr, at the National Institutes of Health in Bethesda, Maryland, where he trained in and conducted research on protein chemistry. A paper on peptide separation and analysis, published in 1959 with Anfinsen, was identified by Current Contents as a Citation Classic.2 He then trained in clinical cardiology with Paul Wood, considered the leading clinical cardiologist of the era, at the Institute of Cardiology in London, followed by a 3-year advanced fellowship in muscle biochemistry with another distinguished scientist, W.F.H.M. Mommarets, at the University of California at Los Angeles (UCLA). Thus, after training in basic science, clinical …

Therapeutic Potential of CRISPR Research Raising Safety and Ethics Questions

CRISPR/Cas9-based genome editing is a potential treatment for Duchenne muscular dystrophy (DMD), according to Charles Gersbach from Duke University in Durham, N.C., and his collaborators there and elsewhere. However, at this stage, that editing is directed to an exon 23 deletion in the mdx model of the disease in mice, with CRISPR/Cas 9-based editing changing “expression of a modified dystrophin gene in place of the defective one, [leading to] partial recovery of functional dystrophin protein in skeletal and cardiac muscle, improvement of muscle biochemistry, and significant enhancement of muscle force,” they report. “This is the first time CRISPR has been successfully delivered throughout the body with a translational approach to treat grown animals with genetic diseases,” points out Christopher Nelson, the lead author of their report that appeared 31 December 2015 in Science (doi:10.1126/science.aad5143).

Changes in muscle biochemistry, myoglobin and cytoglobin in goldfishCarassius auratusexposed to hypoxia-reoxygenation and microcystin RR

AbstractCyanobacterial toxins and oxygen depletion pose serious challenges to aquatic organisms. In this study, the goldfish Carassius auratus was exposed to hypoxia-reoxygenation episodes as well as a cyanobacterial toxin microcystin arginine arginine (MCRR) with an aim of assessing the toxicity of the stressors to muscle biochemistry, cytoglobin mRNA and myoglobin mRNA. The result showed that MCRR and hypoxia-reoxygenation synergistically reduced the total antioxidant capacity of the muscle by over 90%; glutathione peroxidase activity was also significantly reduced in the groups exposed to MCRR and hypoxia (p < 0.05). Sodium ATPase (Na-ATPase) and total ATPase (tATPase) varied from 14.68 ± 2.2 to 27.87 ± 2.0 U/mg protein and were significantly reduced by MCRR (p < 0.005) only. Glucose and protein (sources of energy) were elevated in the muscles of goldfish exposed to MCRR, especially during reoxygenation, although only the latter was significant. Myoglobin and cytoglobin mRNA were not significantly infl...

Beyond body size: muscle biochemistry and body shape explain ontogenetic variation of anti-predatory behaviour in the lizard Salvator merianae.

Anti-predatory behaviour evolves under the strong action of natural selection because the success of individuals avoiding predation essentially defines their fitness. Choice of anti-predatory strategies is defined by prey characteristics as well as environmental temperature. An additional dimension often relegated in this multilevel equation is the ontogenetic component. In the tegu Salvator merianae, adults run away from predators at high temperatures but prefer fighting when it is cold, whereas juveniles exhibit the same flight strategy within a wide thermal range. Here, we integrate physiology and morphology to understand ontogenetic variation in the temperature-dependent shift of anti-predatory behaviour in these lizards. We compiled data for body shape and size, and quantified enzyme activity in hindlimb and head muscles, testing the hypothesis that morphophysiological models explain ontogenetic variation in behavioural associations. Our prediction is that juveniles exhibit body shape and muscle biochemistry that enhance flight strategies. We identified biochemical differences between muscles mainly in the LDH:CS ratio, whereby hindlimb muscles were more glycolytic than the jaw musculature. Juveniles, which often use evasive strategies to avoid predation, have more glycolytic hindlimb muscles and are much smaller when compared with adults 1-2 years old. Ontogenetic differences in body shape were identified but marginally contributed to behavioural variation between juvenile and adult tegus, and variation in anti-predatory behaviour in these lizards resides mainly in associations between body size and muscle biochemistry. Our results are discussed in the ecological context of predator avoidance by individuals differing in body size living at temperature-variable environments, where restrictions imposed by the cold could be compensated by specific phenotypes.

Physiological Adaptations to Training in Competitive Swimming: A Systematic Review.

The purpose of this systematic review was to summarize longitudinal studies on swimming physiology and get implications for daily practice. A computerized search of databases according to the PRISMA statement was employed. Studies were screened for eligibility on inclusion criteria: (i) present two testing points; (ii) on swimming physiology; (iii) using adult elite swimmers; (iv) no case-studies or with small sample sizes. Two independent reviewers used a checklist to assess the methodological quality of the studies. Thirty-four studies selected for analysis were gathered into five main categories: blood composition (n=7), endocrine secretion (n=11), muscle biochemistry (n=7), cardiovascular response (n=8) and the energetic profile (n=14). The mean quality index was 10.58 ± 2.19 points demonstrating an almost perfect agreement between reviewers (K = 0.93). It can be concluded that the mixed findings in the literature are due to the diversity of the experimental designs. Micro variables obtained at the cellular or molecular level are sensitive measures and demonstrate overtraining signs and health symptoms. The improvement of macro variables (i.e. main physiological systems) is limited and may depend on the athletes’ training background and experience.

Migratory preparation associated alterations in pectoralis muscle biochemistry and proteome in Palearctic–Indian emberizid migratory finch, red-headed bunting, Emberiza bruniceps

Avian migration is an exceptionally high-energy-demanding process, which is met by the accumulation and utilization of fuel stores as well as the alterations in muscle physiology prior to their flight. Pre-migratory fattening coupled with changes in flight muscle metabolic enzymes and proteome is required to provide the necessary fuel and muscle performance required for migration. We studied how the serum metabolites (urea, uric acid, and creatinine), pectoralis muscle metabolites (glycogen, glucose, and cholesterol), muscle metabolic enzymes (CPT, HOAD, CS, MDH, CCO, CK, LDH, PFK, MLPL, and PK), liver lipogenic enzyme (FAS), and pectoralis muscle proteins get altered in pre-migratory and non-migratory buntings. Significantly increased pectoralis muscle fatty acid oxidation (CPT and HOAD activity), aerobic/anaerobic capacity (CS, CCO, and MDH activity), glycolytic capacity (PFK and PK activity), lipolysis (muscle LPL), and burst power (CK activity) were observed prior to the spring migration in pre-migratory buntings, whereas significantly increased pectoralis muscle anaerobic capacity (LDH activity) was observed in non-migratory buntings. Significant increase in the liver FAS showed profound lipogenesis prior to the spring migration. In this study, we have also investigated whether muscle has differential protein content during the pre-migratory and non-migratory phases of the annual migratory cycle. Twenty-nine proteins are identified and well characterized varying in expression significantly during the pre-migratory and non-migratory phases.These findings indicate that significant pre-migratory fattening and alterations in flight (pectoralis) muscle biochemistry and proteome in between the non- and pre-migratory phases may play a significant role in pre-migratory flight muscle preparation in these long-route migrants.

Effect of genetic background on the dystrophic phenotype in mdx mice.

Genetic background significantly affects phenotype in multiple mouse models of human diseases, including muscular dystrophy. This phenotypic variability is partly attributed to genetic modifiers that regulate the disease process. Studies have demonstrated that introduction of the γ-sarcoglycan-null allele onto the DBA/2J background confers a more severe muscular dystrophy phenotype than the original strain, demonstrating the presence of genetic modifier loci in the DBA/2J background. To characterize the phenotype of dystrophin deficiency on the DBA/2J background, we created and phenotyped DBA/2J-congenic Dmdmdx mice (D2-mdx) and compared them with the original, C57BL/10ScSn-Dmdmdx (B10-mdx) model. These strains were compared with their respective control strains at multiple time points between 6 and 52 weeks of age. Skeletal and cardiac muscle function, inflammation, regeneration, histology and biochemistry were characterized. We found that D2-mdx mice showed significantly reduced skeletal muscle function as early as 7 weeks and reduced cardiac function by 28 weeks, suggesting that the disease phenotype is more severe than in B10-mdx mice. In addition, D2-mdx mice showed fewer central myonuclei and increased calcifications in the skeletal muscle, heart and diaphragm at 7 weeks, suggesting that their pathology is different from the B10-mdx mice. The new D2-mdx model with an earlier onset and more pronounced dystrophy phenotype may be useful for evaluating therapies that target cardiac and skeletal muscle function in dystrophin-deficient mice. Our data align the D2-mdx with Duchenne muscular dystrophy patients with the LTBP4 genetic modifier, making it one of the few instances of cross-species genetic modifiers of monogenic traits.

Effects of Creatine in Skeletal Muscle Cells and in Myoblasts Differentiating Under Normal or Oxidatively Stressing Conditions.

Creatine (Cr) - along with the Cr kinase (CK) system - plays a fundamental role in muscle biochemistry and physiology not limited to its ergogenic role. Indeed, Cr has been shown to exert pleiotropic effects, which promote protein accretion, muscle-specific protein synthesis, growth in cultured myogenic cells and favour the myogenic process either in normal or stressing conditions. This review focuses on the effects of Cr supplementation on cellular and mitochondrial biochemistry and function in the course of skeletal muscle differentiation, either in normal or oxidatively stressing conditions, and on the ensuing nutraceutical/therapeutic perspectives.

Rapid maturation of the muscle biochemistry that supports diving in Pacific walruses (Odobenus rosmarus divergens).

Physiological constraints dictate animals' ability to exploit habitats. For marine mammals, it is important to quantify physiological limits that influence diving and their ability to alter foraging behaviors. We characterized age-specific dive limits of walruses by measuring anaerobic (acid-buffering capacity) and aerobic (myoglobin content) capacities of the muscles that power hind (longissimus dorsi) and fore (supraspinatus) flipper propulsion. Mean buffering capacities were similar across muscles and age classes (a fetus, five neonatal calves, a 3month old and 20 adults), ranging from 41.31 to 54.14slykes and 42.00 to 46.93slykes in the longissimus and supraspinatus, respectively. Mean myoglobin in the fetus and neonatal calves fell within a narrow range (longissimus: 0.92-1.68 g 100 g(-1) wet muscle mass; supraspinatus: 0.88-1.64 g 100 g(-1) wet muscle mass). By 3 months post-partum, myoglobin in the longissimus increased by 79%, but levels in the supraspinatus remained unaltered. From 3months post-partum to adulthood, myoglobin increased by an additional 26% in the longissimus and increased by 126% in the supraspinatus; myoglobin remained greater in the longissimus compared with the supraspinatus. Walruses are unique among marine mammals because they are born with a mature muscle acid-buffering capacity and attain mature myoglobin content early in life. Despite rapid physiological development, small body size limits the diving capacity of immature walruses and extreme sexual dimorphism reduces the diving capacity of adult females compared with adult males. Thus, free-ranging immature walruses likely exhibit the shortest foraging dives while adult males are capable of the longest foraging dives.

The Assessment of Muscular Effort, Fatigue, and Physiological Adaptation Using EMG and Wavelet Analysis.

Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) is a transcription factor co-activator that helps coordinate mitochondrial biogenesis within skeletal muscle following exercise. While evidence gleaned from submaximal exercise suggests that intracellular pathways associated with the activation of PGC-1α, as well as the expression of PGC-1α itself are activated to a greater extent following higher intensities of exercise, we have recently shown that this effect does not extend to supramaximal exercise, despite corresponding increases in muscle activation amplitude measured with electromyography (EMG). Spectral analyses of EMG data may provide a more in-depth assessment of changes in muscle electrophysiology occurring across different exercise intensities, and therefore the goal of the present study was to apply continuous wavelet transforms (CWTs) to our previous data to comprehensively evaluate: 1) differences in muscle electrophysiological properties at different exercise intensities (i.e. 73%, 100%, and 133% of peak aerobic power), and 2) muscular effort and fatigue across a single interval of exercise at each intensity, in an attempt to shed mechanistic insight into our previous observations that the increase in PGC-1α is dissociated from exercise intensity following supramaximal exercise. In general, the CWTs revealed that localized muscle fatigue was only greater than the 73% condition in the 133% exercise intensity condition, which directly matched the work rate results. Specifically, there were greater drop-offs in frequency, larger changes in burst power, as well as greater changes in burst area under this intensity, which were already observable during the first interval. As a whole, the results from the present study suggest that supramaximal exercise causes extreme localized muscular fatigue, and it is possible that the blunted PGC-1α effects observed in our previous study are the result of fatigue-associated increases in muscle acidosis. This should be explored in future research using further combinations of EMG and muscle biochemistry and histology.

Facing the river gauntlet: understanding the effects of fisheries capture and water temperature on the physiology of coho salmon.

An improved understanding of bycatch mortality can be achieved by complementing field studies with laboratory experiments that use physiological assessments. This study examined the effects of water temperature and the duration of net entanglement on physiological disturbance and recovery in coho salmon (Oncorhynchus kisutch) after release from a simulated beach seine capture. Heart rate was monitored using implanted electrocardiogram biologgers that allowed fish to swim freely before and after release. A subset of fish was recovered in respirometers to monitor metabolic recovery, and separate groups of fish were sacrificed at different times to assess blood and white muscle biochemistry. One hour after release, fish had elevated lactate in muscle and blood plasma, depleted tissue energy stores, and altered osmoregulatory status, particularly in warmer (15 vs. 10°C) and longer (15 vs. 2 min) capture treatments. A significant effect of entanglement duration on blood and muscle metabolites remained after 4 h. Oxygen consumption rate recovered to baseline within 7–10 h. However, recovery of heart rate to routine levels was longer and more variable, with most fish taking over 10 h, and 33% of fish failing to recover within 24 h. There were no significant treatment effects on either oxygen consumption or heart rate recovery. Our results indicate that fishers should minimize handling time for bycatch and maximize oxygen supply during crowding, especially when temperatures are elevated. Physiological data, such as those presented here, can be used to understand mechanisms that underlie bycatch impairment and mortality, and thus inform best practices that ensure the welfare and conservation of affected species.

Architectural and biochemical adaptations in skeletal muscle and bone following rotator cuff injury in a rat model.

Injury to the rotator cuff can cause irreversible changes to the structure and function of the associated muscles and bones. The temporal progression and pathomechanisms associated with these adaptations are unclear. The purpose of this study was to investigate the time course of structural muscle and osseous changes in a rat model of a massive rotator cuff tear. Supraspinatus and infraspinatus muscle architecture and biochemistry and humeral and scapular morphological parameters were measured three days, eight weeks, and sixteen weeks after dual tenotomy with and without chemical paralysis via botulinum toxin A (BTX). Muscle mass and physiological cross-sectional area increased over time in the age-matched control animals, decreased over time in the tenotomy+BTX group, and remained nearly the same in the tenotomy-alone group. Tenotomy+BTX led to increased extracellular collagen in the muscle. Changes in scapular bone morphology were observed in both experimental groups, consistent with reductions in load transmission across the joint. These data suggest that tenotomy alone interferes with normal age-related muscle growth. The addition of chemical paralysis yielded profound structural changes to the muscle and bone, potentially leading to impaired muscle function, increased muscle stiffness, and decreased bone strength. Structural musculoskeletal changes occur after tendon injury, and these changes are severely exacerbated with the addition of neuromuscular compromise.

Syndromes myo-fasciaux du thorax

Myo-fascial syndromes are linked to a ‘compression ignition’ phenomenon in motor endplates of a muscle, called trigger points. The lasting shortening of sarcomeres induce local changes in muscle biochemistry, including acidosis, turning the trigger point from passive to active and making the contraction sustainable. A spinal reflex probably contributes to the maintenance of those painful focal cramps and account for the frequent referred pain, sometimes far away from the original muscle. Myo-fascial disorders can induce pain in the chest leading to anxiety, especially in patients who previously experienced myocardial infarction or surgery for breast cancer, as 50% of those women complain of myo-fascial syndromes of thoracic muscles thereafter. After an overview of the presumed physiopathology of those syndromes, this article focuses on myo-fascial syndromes of pectoralis major, pectoralis minor, abdominal muscles, intercostal muscles and the rare sternal muscle. The lack of definitive evidence about the efficacy of current treatments is stressed, as well as the need to rule out the presence of underlying conditions or differential diagnoses, including thoracic outlet syndromes and entrapment of the distal perforating branches of intercostal nerves.

G.P.194: Intramuscular variation in mitochondrial functionality and sarcoplasmic proteome profile of bovine semimembranosus muscle

Intramuscular variation in the appearance of postmortem bovine semimembranosus has been reported earlier. Although previous research suggested muscle biochemistry as the underlying reason for this phenomenon, limited studies were undertaken in this aspect. We examined the functionality of mitochondria and profile of sarcoplasmic proteome isolated from outside (OSM) and inside (ISM) regions of bovine semimembranosus muscle. Semimembranosus muscles were obtained from eight ( n =8) Bos taurus animals after harvest, and each muscle was separated to ISM and OSM. A randomized complete block design was used in this experiment, where each animal served as a block. Mitochondria were isolated from OSM and ISM, and mitochondrial oxygen consumption was measured with the addition of succinate (40mM) at pH 5.6 and 25°C. Data were analyzed using the Mixed Procedure, and means were separated at p p p

Surface-enhanced Raman spectral biomarkers correlate with Ankle Brachial Index and characterize leg muscle biochemical composition of patients with peripheral arterial disease.

Peripheral arterial disease (PAD) is characterized by atherosclerotic blockages of the arteries supplying the lower extremities, which cause a progressive accumulation of ischemic injury to the skeletal muscles of the lower limbs. This injury includes altered metabolic processes, damaged organelles, and compromised bioenergetics in the affected muscles. The objective of this study was to explore the association of Raman spectral signatures of muscle biochemistry with the severity of atherosclerosis in the legs as determined by the Ankle Brachial Index (ABI) and clinical presentation. We collected muscle biopsies from the gastrocnemius (calf muscle) of five patients with clinically diagnosed claudication, five patients with clinically diagnosed critical limb ischemia (CLI), and five control patients who did not have PAD. A partial least squares regression (PLSR) model was able to predict patient ABI with a correlation coefficient of 0.99 during training and a correlation coefficient of 0.85 using a full cross‐validation. When using the first three PLS factor scores in combination with linear discriminant analysis, the discriminant model was able to correctly classify the control, claudicating, and CLI patients with 100% accuracy, using a full cross‐validation procedure. Raman spectroscopy is capable of detecting and measuring unique biochemical signatures of skeletal muscle. These signatures can discriminate control muscles from PAD muscles and correlate with the ABI and clinical presentation of the PAD patient. Raman spectroscopy provides novel spectral biomarkers that may complement existing methods for diagnosis and monitoring treatment of PAD patients.

Living in the fast lane: rapid development of the locomotor muscle in immature harbor porpoises (Phocoena phocoena).

Cetaceans (dolphins and whales) are born into the aquatic environment and are immediately challenged by the demands of hypoxia and exercise. This should promote rapid development of the muscle biochemistry that supports diving, but previous research on two odontocete (toothed whales and dolphins) species showed protracted postnatal development for myoglobin content and buffering capacity. A minimum of 1 and 1.5years were required for Fraser's (Lagenodelphis hosei) and bottlenose (Tursiops truncatus) dolphins to obtain mature myoglobin contents, respectively; this corresponded to their lengthy 2 and 2.5-year calving intervals (a proxy for the dependency period of cetacean calves). To further examine the correlation between the durations for muscle maturation and maternal dependency, we measured myoglobin content and buffering capacity in the main locomotor muscle (longissimus dorsi) of harbor porpoises (Phocoena phocoena), a species with a comparatively short calving interval (1.5years). We found that at birth, porpoises had 51 and 69% of adult levels for myoglobin and buffering capacity, respectively, demonstrating greater muscle maturity at birth than that found previously for neonatal bottlenose dolphins (10 and 65%, respectively). Porpoises achieved adult levels for myoglobin and buffering capacity by 9-10months and 2-3years postpartum, respectively. This muscle maturation occurred at an earlier age than that found previously for the dolphin species. These results support the observation that variability in the duration for muscular development is associated with disparate life history patterns across odontocetes, suggesting that the pace of muscle maturation is not solely influenced by exposure to hypoxia and exercise. Though the mechanism that drives this variability remains unknown, nonetheless, these results highlight the importance of documenting the species-specific physiological development that limits diving capabilities and ultimately defines habitat utilization patterns across age classes.

Effects of insulin resistance on skeletal muscle growth and exercise capacity in type 2 diabetic mouse models

Type 2 diabetes mellitus is associated with an accelerated muscle loss during aging, decreased muscle function, and increased disability. To better understand the mechanisms causing this muscle deterioration in type 2 diabetes, we assessed muscle weight, exercise capacity, and biochemistry in db/db and TallyHo mice at prediabetic and overtly diabetic ages. Maximum running speeds and muscle weights were already reduced in prediabetic db/db mice when compared with lean controls and more severely reduced in the overtly diabetic db/db mice. In contrast to db/db mice, TallyHo muscle size dramatically increased and maximum running speed was maintained during the progression from prediabetes to overt diabetes. Analysis of mechanisms that may contribute to decreased muscle weight in db/db mice demonstrated that insulin-dependent phosphorylation of enzymes that promote protein synthesis was severely blunted in db/db muscle. In addition, prediabetic (6-wk-old) and diabetic (12-wk-old) db/db muscle exhibited an increase in a marker of proteasomal protein degradation, the level of polyubiquitinated proteins. Chronic treadmill training of db/db mice improved glucose tolerance and exercise capacity, reduced markers of protein degradation, but only mildly increased muscle weight. The differences in muscle phenotype between these models of type 2 diabetes suggest that insulin resistance and chronic hyperglycemia alone are insufficient to rapidly decrease muscle size and function and that the effects of diabetes on muscle growth and function are animal model-dependent.

Regulatory circuits in cell motility

Regulatory Circuits in Cell Motility, a symposium celebration sponsored by the Physiological Society of Philadelphia and the Thomas Jefferson University Department of Molecular Physiology and Biophysics in honor of David Hartshorne and his many contributions to muscle research was held at Jefferson Medical College, Thomas Jefferson University in Philadelphia on October 11–12, 2013. Drs. Marion Siegman, Masumi Eto, Mike Walsh, Feri Erdodi, Tim Haystead and Avril Somlyo served on the Organizing Committee. Many colleagues and muscle researchers from Europe, Japan, Canada and the USA attended this meeting in recognition of Dr. Hartshorne’s seminal contributions to the biochemistry and physiology of muscle proteins over a stellar career. Dr. Hartshorne trained under the mentorship of the renowned Sam Perry at the University of Birmingham, England where he received his Ph.D. in Muscle Biochemistry in 1962. Following postdoctoral training at UCSF, SUNY Brooklyn and the University of Birmingham, he accepted a position as Assistant Professor of Chemistry at Carnegie-Mellon University rising through the ranks to Professor. Subsequently, he moved to Tucson at the University of Arizona where his laboratory attracted many young international muscle biochemists and physiologists. He has recently retired to enjoy the Tucson sunshine. Apart from his early work on troponin, tropomyosin and the subunit structure of myosin, Dave is recognized for his groundbreaking contributions to the understanding of the role of myosin regulatory light chain phosphorylation as the switch to activate smooth muscle myosin actomyosin ATPase as well as the importance of calmodulin as a regulatory component of myosin light chain kinase. He is also recognized for his major studies on myosin phosphatases and their regulation by phosphorylation in smooth muscle contractility, in mitosis and cell motility. His discovery of calyculin A as an inhibitor of type 1 and 2A protein serine/threonine phosphatases has provided an excellent tool for the field. The symposium covered the following areas: myosin light chain kinases and the roles of myosin light chain phosphorylation; regulation and function of myosin light chain phosphatase; calcium sensitization and desensitization; calmodulin, twitchin, phosphatase targeting and actin polymerization; unconventional myosins. Speaker and poster abstracts follow.