Muscle Resistance Research Articles

Effect of yoga intervention on skeletal muscle linked glucose homeostasis in pre-diabetic individuals: Study protocol for a randomized controlled trial

BackgroundThe pre-diabetic stage is important in terms of identification and timely management due to its reversible nature. Along with other factors, insulin resistance in skeletal muscle is often considered as primary defect before development of overt hyperglycemia and Diabetes Mellitus (DM). Physical exercises are beneficial in prevention of DM by improving skeletal muscle mediated glucose metabolism. Evidence suggests that Yoga interventions appear to be equal and/or superior to exercise in most outcome measures. As the Yogic postures are relatable to exercises, they are considered to improve skeletal muscle function and reverse the pre-diabetic stage. MethodsThis open-labelled, randomized clinical study is planned to evaluate effect of Yoga interventions on muscle mass, strength, endurance and flexibility which are direct/indirect indicators of fat deposition in skeletal muscles. Association between changes in muscle quality/ functionality and glycemic control will also be explored. With ethics committee permission, 120 pre-diabetic individuals of either sex between age group of 35–49 years with BMI range of 25–35 kg/m2 and family history of Type 2 Diabetes Mellitus (T2DM) will be recruited after obtaining written informed consent. They will be randomly allocated to either Yoga or exercise group by computer generated randomized method in a 1:1 ratio. One group will receive defined Yoga interventions, while other group will receive fixed program of physical exercises. Prior to initiating this 12-week study, both groups will undergo a training session for 4 weeks under supervision of a trained instructor. The outcome measures will be parameters related to muscle quality/functionality and glucose metabolism markers. DiscussionOur study aims to explore practicality of Yoga in pre-diabetic stage on skeletal muscle related glycemic control, which is novel. Additionally, the study will generate awareness about pre-diabetes and provide people with active coping skills for reversing it.

Muscle cytotoxicity and immuno-reactivity analysis of the porous carbon nanospheres fabricated by high temperature calcination

Carbon-based nanomaterials have a high specific surface area, biocompatibility, and controlled mesopore structures. These characteristics make carbon nanospheres excellent carriers for drugs, biological dyes, photosensitizers, etc. Nevertheless, little is known about the impact of topological features on the surface of carbon nanomaterials on their in vivo immunoreactivity. In this study, we fabricated mesoporous carbon nanoparticles (MCNs) and solvent-processable carbon vesicles (CVs) by high-temperature calcination. The hematoxylin and eosin (H&E) staining suggested CVs' relatively poor dispersion capacity compared to MCNs and carbon precursors (CPs), leading to more severe muscle inflammation and necrosis. Immunostaining and Fluorescence Activated Cell Sorter (FACS) analysis further showed that both MCNs and CVs triggered a transient immune response in transplanted muscle and muscle-draining lymph nodes, but did not alter muscle resistance to exogenous viruses. In conclusion, this study provides insights into how carbon nanoparticles modulate the activation of immune responses in vivo.

Disrupting circadian control of peripheral myogenic reactivity mitigates cardiac injury following myocardial infarction.

Circadian rhythms orchestrate important functions in the cardiovascular system: the contribution of microvascular rhythms to cardiovascular disease progression/severity is unknown. This study hypothesized that (i) myogenic reactivity in skeletal muscle resistance arteries is rhythmic and (ii) disrupting this rhythmicity would alter cardiac injury post-myocardial infarction (MI). Cremaster skeletal muscle resistance arteries were isolated and assessed using standard pressure myography. Circadian rhythmicity was globally disrupted with the ClockΔ19/Δ19 mutation or discretely through smooth muscle cell-specific Bmal1 deletion (Sm-Bmal1 KO). Cardiac structure and function were determined by echocardiographic, hemodynamic and histological assessments. Myogenic reactivity in cremaster muscle resistance arteries is rhythmic. This rhythm is putatively mediated by the circadian modulation of a mechanosensitive signalosome incorporating tumour necrosis factor and casein kinase 1. Following left anterior descending coronary artery ligation, myogenic responsiveness is locked at the circadian maximum, although circadian molecular clock gene expression cycles normally. Disrupting the molecular clock abolishes myogenic rhythmicity: myogenic tone is suspended at the circadian minimum and is no longer augmented by MI. The reduced myogenic tone in ClockΔ19/Δ19 mice and Sm-Bmal1 KO mice associates with reduced total peripheral resistance (TPR), improved cardiac function and reduced infarct expansion post-MI. Augmented microvascular constriction aggravates cardiac injury post-MI. Following MI, skeletal muscle resistance artery myogenic reactivity increases specifically within the rest phase, when TPR would normally decline. Disrupting the circadian clock interrupts the MI-induced augmentation in myogenic reactivity: therapeutics targeting the molecular clock, therefore, may be useful for improving MI outcomes.

The Effects of Dietary Supplements, Nutraceutical Agents, and Physical Exercise on Myostatin Levels: Hope or Hype?

Myostatin, a secreted growth factor belonging to the transforming growth factor β (TGF-β) family, performs a role in hindering muscle growth by inhibiting protein kinase B (Akt) phosphorylation and the associated activation of hypertrophy pathways (e.g., IGF-1/PI3K/Akt/mTOR pathway). In addition to pharmacological agents, some supplements and nutraceutical agents have demonstrated modulatory effects on myostatin levels; however, the clinical magnitude must be appraised with skepticism before translating the mechanistic effects into muscle hypertrophy outcomes. Here, we review the effects of dietary supplements, nutraceutical agents, and physical exercise on myostatin levels, addressing the promise and pitfalls of relevant randomized clinical trials (RCTs) to draw clinical conclusions. RCTs involving both clinical and sports populations were considered, along with wasting muscle disorders (e.g., sarcopenia) and resistance training-induced muscle hypertrophy, irrespective of disease status. Animal models were considered only to expand the mechanisms of action, and observational data were consulted to elucidate potential cutoff values. Collectively, the effects of dietary supplements, nutraceutical agents, and physical exercise on myostatin mRNA expression in skeletal muscle and serum myostatin levels are not uniform, and there may be reductions, increases, or neutral effects. Large amounts of research using resistance protocols shows that supplements or functional foods do not clearly outperform placebo for modulating myostatin levels. Thus, despite some biological hope in using supplements or certain functional foods to decrease myostatin levels, caution must be exercised not to propagate the hope of the food supplement market, select health professionals, and laypeople.

Insulin sensitivity is preserved in mice made obese by feeding a high starch diet.

Obesity is generally associated with insulin resistance in liver and muscle and increased risk of developing type 2 diabetes, however there is a population of obese people that remain insulin sensitive. Similarly, recent work suggests that mice fed high carbohydrate diets can become obese without apparent glucose intolerance. To investigate this phenomenon further, we fed mice either a high fat (Hi-F) or high starch (Hi-ST) diet and measured adiposity, glucose tolerance, insulin sensitivity, and tissue lipids compared to control mice fed a standard laboratory chow. Both Hi-ST and Hi-F mice accumulated a similar amount of fat and tissue triglyceride compared to chow-fed mice. However, while Hi-F diet mice developed glucose intolerance as well as liver and muscle insulin resistance (assessed via euglycaemic/hyperinsulinaemic clamp), obese Hi-ST mice maintained glucose tolerance and insulin action similar to lean, chow-fed controls. This preservation of insulin action despite obesity in Hi-ST mice was associated with differences in de novo lipogenesis and levels of C22:0 ceramide in liver and C18:0 ceramide in muscle. This indicates that dietary manipulation can influence insulin action independently of the level of adiposity and that the presence of specific ceramide species correlates with these differences.

Factors associated with poor long-term adherence after completing a pulmonary rehabilitation programme in patients with chronic obstructive pulmonary disease.

Although pulmonary rehabilitation programmes (PRPs) benefit patients with chronic obstructive pulmonary disease (COPD), poor adherence to these programmes is common. This study aimed to analyse the factors associated with poor long-term adherence after completing a PRP. We conducted a retrospective study of 70 patients with COPD who performed an 8-week outpatient PRP that included 24 sessions of aerobic training, skeletal muscle resistance exercises, physiotherapy and COPD education. The study classified the patients into 2 groups: (1) long-term adherence and (2) long-term non-adherence to the PRP. We considered long-term non-adherence when the patient did not attend the 32 weeks follow-up visit after beginning the PRP. We measured the degree of dyspnoea, quality of life, physical activity, anxiety-depression status, submaximal exercise capacity and COPD exacerbations in both groups. The patients' median age was 69.6 [63.8-75.0] years, and 71.4% were men. The median forced expiratory volume in 1 second was 60.0 [47.7-68.0] % of that predicted. We observed total COPD exacerbations and severe COPD exacerbations in the last year in 32 (45.7%) and 22 (31.4%) patients, respectively. Dyspnoea, physical activity and quality of life significantly improved after completing the PRP. Long-term non-adherence to the PRP was observed in 32 (45.7%) patients. In the single regression model, severe COPD exacerbations (p = 0.04) and dyspnoea (p = 0.03) were associated with long-term non-adherence to the PRP. In the multiple regression model, only severe COPD exacerbations remained as an associated factor (OR 2.7; 95% CI 1.1-8,1; p = 0.04). Approximately half of patients who complete PRPs present long-term non-adherence to the programme. Severe COPD exacerbations are associated with long-term non-adherence.

Botulinum Toxin Intervention in Cerebral Palsy-Induced Spasticity Management: Projected and Contradictory Effects on Skeletal Muscles.

Spasticity, following the neurological disorder of cerebral palsy (CP), describes a pathological condition, the central feature of which is involuntary and prolonged muscle contraction. The persistent resistance of spastic muscles to stretching is often followed by structural and mechanical changes in musculature. This leads to functional limitations at the respective joint. Focal injection of botulinum toxin type-A (BTX-A) is effectively used to manage spasticity and improve the quality of life of the patients. By blocking acetylcholine release at the neuromuscular junction and causing temporary muscle paralysis, BTX-A aims to reduce spasticity and hereby improve joint function. However, recent studies have indicated some contradictory effects such as increased muscle stiffness or a narrower range of active force production. The potential of these toxin- and atrophy-related alterations in worsening the condition of spastic muscles that are already subjected to changes should be further investigated and quantified. By focusing on the effects of BTX-A on muscle biomechanics and overall function in children with CP, this review deals with which of these goals have been achieved and to what extent, and what can await us in the future.

Performing the classification of pulsation cardiac beats automatically by using CNN with various dimensions of kernels

The clinical indication of arrhythmia identifies specific aberrant circumstances in heart pumping that may be detected using electrical impulses during conduction or by allowing a little amount of current to travel through the electrodes, disrupting the cardiac muscle's resistance. The electrocardiogram (ECG) is one of the most important instruments for detecting cardiac arrhythmia since it is the most least intrusive and effective procedure. Physically or visually inspecting the heart is time-consuming and difficult, hence the development of computer aided diagnosis (CAD) is being developed to aid clinical decision-making. In this suggested research, a convolutional neural network (CNN)-based approach is used to automate the heartbeat classification process in order to identify cardiac arrhythmia. The improved enhancement of CNN structure has been implemented in this suggested research. The feature maps are then subjected to the max pooling process. Finally, feature maps are generated by concatenating kernels of different sizes and delivering them as an input to the fully linked layers. The MIT BIH arrhythmia database is used to implement this approach, and the total average accuracy is 99.21%. The proof of the suggested study's efficiency and efficacy in identifying cardiac arrhythmia has also been done via an experimental comparison

RF04 | PSUN334 Mineralocorticoid receptors mediate diet - induced lipid infiltration of skeletal muscle and insulin resistance

Abstract Excess blood lipids increase the total intramyocellular (IMC) lipid content and ectopic fat storage resulting in lipotoxicity and insulin resistance in skeletal muscle, which is one of the main targets of insulin whose action is central for the maintenance of glucose homeostasis. Consumption of a diet high in fat and refined sugars, a Western Diet (WD), has been shown to activate mineralocorticoid receptors (MRs) to promote insulin resistance. However, our understanding of the precise mechanisms by which enhanced MR activation promotes skeletal muscle insulin resistance remains unclear. In this study we investigated the roles and mechanisms by which enhanced MR signaling in soleus muscle promotes ectopic lipid accumulation and related insulin resistance in diet-induced obesity. Six week-old C57BL6J mice were fed either a mouse chow diet or WD with or without spironolactone (1 mg/kg/day) for 16 weeks. Spironolactone attenuated 16 weeks of WD - induced in vivo glucose intolerance and improved soleus insulin metabolic signaling (protein kinase B and AMP kinase α pathways). Improved insulin sensitivity was accompanied by increased Glut-4 expression in conjunction with decreased IMC lipid content and reduced free fatty acid (FFA) levels and CD36 expression in soleus skeletal muscle tissue. Related to this, miR-99a was identified to negatively target CD36(www.targetscan.org/vert_72/) and elevated CD36 induced excessive FFA uptake, ectopic lipid accumulation, as well as systemic and tissue insulin resistance. Furthermore, in skeletal muscle cells spironolactone prevented enhanced MR signaling mediated reduction of miR-99a and related increased CD36. These data indicate that inhibition of MR activation with spironolactone reversed diet - induced reduction of miR-99a, thereby reducing CD36 expression, leading to reduced IMC lipid content and improved soleus insulin sensitivity. Presentation: Saturday, June 11, 2022 1:48 p.m. - 1:53 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Control of blood pressure in the cold: differentiation of skin and skeletal muscle vascular resistance.

What is the central question of this study? Why does blood pressure increases during cold air exposure? Specifically, what is the contribution of skin and skeletal muscle vascular resistance during whole body versus isolated face cooling? What is the main finding and its importance? Whole-body cooling caused an increase in blood pressure through an increase in skeletal muscle and cutaneous vascular resistance. However, isolated mild face cooling caused an increase in blood pressure predominately via an increase in cutaneous vasoconstriction. The primary aim of this investigation was to determine the individual contribution of the cutaneous and skeletal muscle circulations to the cold-induced pressor response. To address this, we examined local vascular resistances in the cutaneous and skeletal muscle of the arm and leg. Thirty-four healthy individuals underwent three different protocols, whereby cold air to clamp skin temperature (27°C) was passed over (1) the whole-body, (2) the whole-body, but with the forearm pre-cooled to clamp cutaneous vascular resistance, and (3) the face. Cold exposure applied to the whole body or isolated to the face increased mean arterial pressure (all, P<0.001) and total peripheral resistance (all, P<0.047) compared to thermal neutral baseline. Whole-body cooling increased femoral (P<0.005) and brachial artery resistance (P<0.003) compared to thermoneutral baseline. Moreover, when the forearm was pre-cooled to remove the contribution of cutaneous resistance (P=0.991), there was a further increase in lower arm vasoconstriction (P=0.036) when whole-body cooling was superimposed. Face cooling also caused a reflex increase in lower arm cutaneous (P=0.009) and brachial resistance (P=0.050), yet there was no change in femoral resistance (P=0.815) despite a reflex increase in leg cutaneous resistance (P=0.010). Cold stress causes an increase in blood pressure through a change in total peripheral resistance that is largely due to cutaneous vasoconstriction with face cooling, but there is additional vasoconstriction in the skeletal muscle vasculature with whole-body cooling.

A20 (TNFAIP3) Knockdown Protects from Abdominal Aortic Aneurysms by Promoting Smooth Muscle Cell Differentiation and Resistance to Apoptosis

Introduction: The implication of inflammation in the pathogenesis of abdominal aortic aneurysms (AAA) remains unresolved. Our laboratory has previously established the potent atheroprotective properties of the anti-inflammatory gene A20. In this study, we investigated A20’s implication in the development of AAA. Methods: Aneurysms were induced by periadventitial application of elastase to the infrarenal aorta of 10-week-old A20 wild-type (WT) and A20-deficient heterozygous (Het) C57BL/6 mice supplemented with 0.2% BAPN drinking water. Aortic diameter was measured by ultrasound before and 28 days (d) after. Aortae were harvested at 28d for morphology, immunohistochemistry (IHC) and molecular profiling (qPCR). Results: Het mice were protected from AAA formation. Percent increase in aortic diameter was significantly lower in Het vs WT mice (<50% vs >120%, n = 13-17, p < 0.01). At the molecular level, protection from AAA in Het vs WT aortae corresponded with significantly i) higher levels of TGFβ (qPCR, n = 17-18, p < 0.01), a promoter of SMC differentiation, and downstream SMAD3 phosphorylation (IHC, n = 5; p < 0.0001); and ii) reduced rate of SMC apoptosis (TUNEL, n = 4, p < 0.01). As anticipated, knockdown of A20, a potent inhibitor of NF-κB and IFNγ signaling, significantly increased mRNA levels of the inflammatory markers IκBα, p65, MCP1, IFNγ, and IP10 in Het vs WT (n = 17-18, p < 0.05). Conclusion: This is the first report that A20 knockdown protects from AAA by increasing TGFβ signaling and reducing SMC apoptosis, despite promoting inflammation. Pilot studies validate that A20 polymorphisms lowering its expression slow AAA progression, supporting our pursuit of A20-siRNA gene therapies.

The impact of an exercise intervention using low-cost equipment on functional fitness in the community-dwelling older adults: A pilot study.

Exercise interventions have shown significant improvements in the older adult population regarding functional and cognitive capacity. However, much research has applied exercise protocols that are expensive both for research and participation. Thus, high investments that are made are currently not ecologically efficient. The aim of the study was to determine whether the impact of a 20-week multicomponent exercise intervention using low-cost material could improve physical fitness in community-dwelling older adults. We tested the feasibility of this three times per week exercise protocol using an inclusive approach. Eligibility criteria included age ≥65years, the ability to stand and walk with or without assistive devices, being physically inactive; medical clearance, and living in the community. Outcomes were muscle resistance measured using the chair-stand test for lower limbs, cardiorespiratory capacity measured using the 6-min walk test, and agility and balance using the Timed-up and Go test. Flexibility was measured using the chair sit and reach for lower limbs and the back scratch for upper limbs using the dominant leg and arm, respectively. Hand grip strength was measured using a dynamometer. Thirty participants (n = 30) were recruited and included in the intention-to-treat analysis. The mean age of participants was 70years (±3.62years), 100% were Caucasians, and 50% were female. There was a significant trend toward a clinically important improvement in the chair-stand (t = -5.23; p < 0.001; d = 0.36), arm curl (t = -5.21; p < 0.001; d = 0.74), 6-min walk test (t = -4.69; p = <0.001; d = 0.77), timed-up and go test (t = 8.788; p < 0.001; d = 1.18), and hand grip strength (t = 2.846; p = 0.009; d = 0.23). There were also differences in the back scratch (t = 2.243; p = 0.035; d = 0.29) and chair sit and reach test (t = -3.380; p < 0.001; d = 0.15). This pilot study has provided preliminary evidence that a 20-week community-based low-cost exercise program may be effective in improving overall functional fitness in older people. The pilot trial has provided the necessary data to design future randomized-controlled trials that can be implemented in the community in an ecological feasible manner.

Effect of Intermittent Fasting on Muscle Glycogen Stores in Rats with High-Calorie Diet

Insulin resistance in skeletal muscle is important since it is normally responsible for most of the insulin-mediated glucose disposal and contains the largest glycogen storage regulated by insulin sensitivity. A high-calorie diet is known to be a risk factor for insulin resistance. Lifestyle modification by regulating caloric intake through intermittent fasting (IF) is recommended to prevent insulin resistance. This study aims to analyze the effect of eight weeks of intermittent fasting on skeletal muscle glycogen stores in rats with a four-week high-calorie diet. A total 24 healthy male Wistar rats were divided into four groups, Ad-libitum with a standard diet (AL-SD) Ad-libitum with a high-calorie diet (AL-HCD) IF with a standard diet (IF-SD) IF with a high-calorie diet (IF-HCD). Muscles were obtained and stained with PAS stain to evaluate glycogen expression based on color intensity. The results of the glycogen expression score were obtained as follows, AL-SD=2.113±0.589 AL-HCD=1.827±0.375 IF-SD=2.109±0.499 IF-HCD=1.979±0.334. Although there was no significant difference between groups (p> 0.05), IF can prevent excessive reduction of glycogen stores in subjects with a HCD compared to the AL-HCD group. In conclusion, this study suggests that IF might improve the reduction of glycogen stores in muscles due to a high-calorie diet.

Black phosphorus quantum dots cause glucose metabolism disorder and insulin resistance in mice

Black phosphorus quantum dots (BPQDs) are considered to have wide application prospects due to their excellent properties. However, there is no study on the effect of BPQDs on glucose metabolism. In this study, blood glucose was significantly increased when mice were continuously intragastrically administered 0.1 and 1 mg/kg bw BPQDs. The blood glucose level of the mice was elevated from Day 7 to Day 28. BPQD exposure also decreased the area under the curve (AUC) of the oral glucose tolerance test (OGTT). After exposure, the pancreas somatic index was increased. Moreover, the serum insulin and glucagon levels were elevated and the relative area of islet β cells was increased in BPQD-exposed mice, while insulin signaling cascades were reduced in muscle tissues. In summary, our study demonstrated for the first time that BPQD exposure induces glucose disorder and insulin resistance in muscle, which is helpful to understand the biosafety of black phosphorus nanomaterials and promote the sustainable development of nanotechnology.

Kaempferol 3-O-rutinoside from Antidesma acidum Retz. Stimulates glucose uptake through SIRT1 induction followed by GLUT4 translocation in skeletal muscle L6 cells

Ethnopharmacological relevanceAntidesma acidum Retz, a perennial herb is known for its anti-diabetic potential among the traditional health care providers of the tribal communities of Manipur, India. Scientific validation of the ancient knowledge on traditional use of this plant with the help of modern tools and techniques can promote further research and its use in health care. Aim of the studyType 2 Diabetes (T2D) is a complex metabolic disorder and linked with hyperglycemia occurring from insufficiency in insulin secretion, action, or both. The aim of this study was to scientifically validate the traditional myth behind the uses of this plant material against diabetes. More specifically, it was aimed to determine the effect of methanolic extract of A. acidum leaves and/or any of its bioactive phytochemical(s), in enhancing insulin sensitization and subsequently stimulating the insulin signaling cascade of glucose metabolism. Materials and methodsMethanol was used for extraction from the leaf powder of A. acidum followed by bioactivity guided fractionation and isolation of most active component. Biological evaluation was performed to determine the glucose uptake ability against insulin resistance in skeletal muscle (L6) cells. To understand the detailed mechanism of actions of the purified compound, several molecular biology and structural biology experiments such as Western blot, siRNA transfection assay and molecular docking study were performed. Results and discussionBioactivity guided isolation of pure compound and spectral data analysis led us to identify the active component as Kaempferol 3-O-rutinoside (KOR) for the first time from the leaf of A. acidum. Over expression of NAD-dependent histone deacetylase, Sirtuin 1 (SIRT1) was observed following KOR treatment. SIRT1 plays an important role in the metabolic pathway and over expression of SIRT implies that it involves in insulin signaling directly or indirectly. Molecular docking and simulation study showed the strong involvement between KOR and SIRT1.Treatment with KOR resulted in significant over expression of SIRT1followed by upregulation of insulin-dependent p-IRS, AKT and AMPK signaling molecules, and stimulation of the GLUT4 translocation, which ultimately enhanced the glucose uptake in sodium palmitate-treated insulin resistant L6 myotubes. Further, the effect of KOR on IRS1, AKT and AMPK phosphorylation, GLUT4 translocation, and glucose uptake was attenuated in SIRT1-knockdown myotubes. ConclusionOverall, the results of this study suggest that Kaempferol 3-O-rutinoside is the active component presents in the leaf of A. acidum which increases glucose consumption by inducing SIRT1 activation and consequently improves insulin sensitization. These results may find future applications in drug discovery research against T2DM.

Effect of Carica papaya on IRS-1/Akt Signaling Mechanisms in High-Fat-Diet-Streptozotocin-Induced Type 2 Diabetic Experimental Rats: A Mechanistic Approach.

Despite rigorous endeavors, existing attempts to handle type 2 diabetes (T2DM) are still a long way off, as a substantial number of patients do not meet therapeutic targets. Insulin resistance in skeletal muscle is discerned as a forerunner in the pathogenesis of T2DM and can be detected years before its progress. Studies have revealed the antidiabetic properties of Carica papaya (C. papaya), but its molecular mechanism on insulin receptor substrate-1 (IRS-1)/Akt signaling mechanisms is not yet known. The present study aimed to evaluate the role of C. papaya on IRS1 and Akt in high-fat-diet–streptozotocin-induced type 2 diabetic rats and also to analyze the bioactive compounds of C. papaya against IRS-1 and Akt via in silico analysis. Ethanolic extract of the leaves of C. papaya (600 mg/kg of body weight) was given daily for 45 days postinduction of T2DM up to the end of the study. Gluconeogenic enzymes, glycolytic enzymes, gene expression, and immunohistochemical analysis of IRS-1 and Akt in skeletal muscle were evaluated. C. papaya treatment regulated the levels of gluconeogenic and glycolytic enzymes and the levels of IRS-1 and Akt in skeletal muscle of type 2 diabetic animals. In silico studies showed that trans-ferulic acid had the greatest hit rate against the protein targets IRS-1 and Akt. C. papaya restored the normoglycemic effect in diabetic skeletal muscle by accelerating the expression of IRS-1 and Akt.

Naringin Ameliorates Skeletal Muscle Atrophy and Improves Insulin Resistance in High-Fat-Diet-Induced Insulin Resistance in Obese Rats.

Obesity causes progressive lipid accumulation and insulin resistance within muscle cells and affects skeletal muscle fibres and muscle mass that demonstrates atrophy and dysfunction. This study investigated the effects of naringin on the metabolic processes of skeletal muscle in obese rats. Male Sprague Dawley rats were divided into five groups: the control group with normal diet and the obese groups, which were induced with a high-fat diet (HFD) for the first 4 weeks and then treated with 40 mg/kg of simvastatin and 50 and 100 mg/kg of naringin from week 4 to 8. The naringin-treated group showed reduced body weight, biochemical parameters, and the mRNA expressions of protein degradation. Moreover, increased levels of antioxidant enzymes, glycogen, glucose uptake, the expression of the insulin receptor substrate 1 (IRS-1), the glucose transporter type 4 (GLUT4), and the mRNA expressions of protein synthesis led to improved muscle mass in the naringin-treated groups. The in vitro part showed the inhibitory effects of naringin on digestive enzymes related to lipid and glucose homeostasis. This study demonstrates the potential benefits of naringin as a supplement for treating muscle abnormalities in obese rats by modulating the antioxidative status, regulating protein metabolism, and improved insulin resistance in skeletal muscle of HFD-induced insulin resistance in obese rats.

Role of Exosomes Derived from Adipose Tissue under Obese Conditions in Skeletal Muscle and Liver Cells: Commonalities and Differences.

To determine the correlation between obesity and insulin resistance in skeletal muscle and liver tissues, this study isolates exosomes from adipose tissue under obese conditions and investigates the effect of adipose tissue-derived exosomes (Ad-exosomes) in mouse muscle (C2C12 cells) and liver cell lines (AML12 cells). The study isolates exosomes from the adipose tissue of normal diet-fed mice or high-fat diet (HFD)-fed obese mice and confirms the uptake into differentiated C2C12 and AML12 cells. Ad-exosomes from HFD-fed mice induce insulin resistance, triglyceride (TG) accumulation, endoplasmic reticulum stress, and inflammation in both C2C12 and AML12 cells. Interestingly, the study finds that the TG accumulation induces by Ad-exosomes from HFD-fed obese mice is dramatically increased in AML12 cells compared with that in the differentiated C2C12 cells, and glucose uptake following the same treatment is decreased in C2C12 cells and increased in AML12 cells. In addition, Ad-exosomes from HFD-fed obese mice cause not only TG accumulation but also lipogenesis in AML12 cells. The results suggest that Ad-exosomes from HFD-fed obese mice cause insulin resistance in both the muscles and liver, but their effects on metabolism during the development of insulin resistance vary between tissues.

Oxidative Stress as a Contributor to Insulin Resistance in the Skeletal Muscles of Mice with Polycystic Ovary Syndrome.

Polycystic ovarian syndrome (PCOS) is a reproductive, endocrine, and metabolic disorder. Circulating markers of oxidative stress are abnormal in women with PCOS. There is a close relationship between oxidative stress and insulin resistance (IR). However, little information is available about oxidative stress in the skeletal muscles of those affected by PCOS. In this study, PCOS was induced in prepubertal C57BL/6J mice by injection with dehydroepiandrosterone. Oxidative stress biomarkers were then measured in both serum and skeletal muscles. The underlying mechanisms were investigated in C2C12 myotubes treated with testosterone (T). We discovered increased oxidative biomarkers, increased ROS production, and damaged insulin sensitivity in the skeletal muscles of mice with PCOS. High levels of T caused mitochondrial dysfunction and increased ROS levels through the androgen receptor (AR)-nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) signaling pathway in C2C12 cells. Treatment of C2C12 cells with an antioxidant N-acetylcysteine (NAC) decreased T-induced ROS production, improved mitochondrial function, and reversed IR. Administration of NAC to mice with PCOS improved insulin sensitivity in the skeletal muscles of the animals. Hyperandrogenism caused mitochondrial dysfunction and redox imbalance in the skeletal muscles of mice with PCOS. We discovered that oxidative stress contributed to skeletal muscle IR in PCOS. Reducing ROS levels may improve the insulin sensitivity of skeletal muscles in patients with PCOS.

Proprioception and Geriatric Low Back Pain.

Proprioception is a deep sensation that perceives the position of each part of the body, state of movement and muscle contraction, and resistance and mass applied to the body. Proprioceptive feedback influences movement and positional accuracy, resulting in key somatosensory functions for human postural control. Proprioception encompasses signals received from proprioceptors located in the skin, subcutaneous tissue, muscles, tendons, and joint capsules, commonly known as mechanoreceptors. The muscle spindle, a crucial proprioceptor, is stretched during eccentric contraction of muscle, thus generating an action potential on afferent fibers to convey a proprioceptive information to the sensorimotor cortex in the brain. For exercise therapy in patients with locomotor disease, proprioception serves an essential function for motor control; thus, this should be considered to obtain effective muscle output. As postural control is achieved by proprioceptive function according to the balance between the lower limb and trunk, relative proprioceptive weighting ratio can help clarify proprioceptive control using muscle response to mechanical vibration. The absence of proprioceptive information congruent with motor intention activates cortical center monitoring incongruence of sensation, leading to pathological pain. Therapeutic procedures may aim to restore the integrity of cortical information processing in musculoskeletal chronic pain. Poor proprioception is one of the main causes of decreased postural balance control in elderly patients with low back pain (LBP). It has been hypothesized that proprioception of the lower limbs deteriorates with age-related muscle mass loss (sarcopenia), which increases the proprioceptive burden on the lumbar spine. Accurate diagnosis of the proprioceptive function is important for establishing a treatment procedure for proprioceptive recovery, and further prospective research is required to clarify the relationship between proprioception and LBP improvement.