Rat Soleus Research Articles

Beneficial effects of the SGLT2 inhibition on oxidative skeletal muscle in infarcted rats

Abstract Introduction Metabolic, morphological, and biochemical changes in skeletal muscle are common in chronic heart failure patients. Despite the cardioprotective effects of sodium-glucose co-transporter 2 (SGLT2) inhibition in heart failure, the impact of this drug on skeletal muscle remains poorly understood. This study investigated the effects of SGLT2 inhibitor empagliflozin (EMPA) on the soleus muscle of rats with myocardial infarction (MI)-induced heart failure. Methods One week after MI induction, male Wistar rats were divided into Sham (n=10), Sham+EMPA (n=12), MI (n=10) and MI+EMPA (n=09) groups. EMPA was added to rat chow (5 mg/kg/day) for 12 weeks. Cardiac remodeling was evaluated by echocardiogram. Enzymatic activity and oxidative stress marker concentrations were assessed by spectrophotometry; protein expression was evaluated by Western blotting. After histological analysis of the left ventricle (LV), only rats with MI greater than 35% of total LV area were included in the study. Statistical analysis: ANOVA and Tukey or Kruskal–Wallis and Dunn and t test; p<0.05. Results Infarction size did not differ between groups. Infarcted groups had larger LV systolic and diastolic diameters, LV diastolic area (Sham 47±7.1; Sham+EMPA 48±4.5; MI 100±16.1*; MI+EMPA 85±10.1#† mm2; p<0.05: * vs Sham; # vs Sham+EMPA; † vs MI), and left atrial diameter (Sham 5.62±0.2; Sham+EMPA 5.65±0.3; MI 7.69±1.3*; MI+EMPA 6.85±0.9#† mm; p<0.05: * vs Sham; # vs Sham+EMPA; † vs MI); and lower LV posterior wall shortening velocity and ejection fraction than control groups. Echocardiographic changes were attenuated in MI+EMPA compared to MI. Other results are shown in Picture 1. Conclusion SGLT2 inhibitor empagliflozin attenuates infarction-induced cardiac remodeling in rats. Empagliflozin prevents increase in oxidative stress, modulates protein turnover by IGF-1 pathway, and attenuates morphological and biochemical changes in the soleus muscle of infarcted rats.

Alterations in FoxO3a, NF-κB, and MuRF1 Expression in the Soleus Muscle of Male Rats Following High-Intensity Interval Training and Detraining.

Activation of the transcription factors FoxO3a and NF-κB is necessary for muscle atrophy, which occurs during cancer cachexia and detraining. It is not known how high-intensity interval training (HIIT) and detraining affect activation of these pathways. Two-month-old male Sprague-Dawley rats were assigned to sedentary control (SC) (n = 6) and HIIT (HIIT) (n = 18) groups. The HIIT group was divided into three subgroups: HIIT (n = 6), HIIT + 7-day detraining (n = 6), and HIIT + 14-day detraining (n = 6). The expression of FoxO3a, NF-κB, MuRF1, and PGC-1α in the soleus muscle was examined by RT-PCR using CYBR Green. The 2-Ct, Livak method was used to calculate the changes in data expression. The soleus muscle mass increased after HIIT (35.10%) and decreased after 7- and 14-day of detraining (15 and 21%, respectively). The mRNA expression levels of NF-κB, MuRF1, and PGC1α in the soleus muscle were upregulated, and FoxO3a levels were significantly lower in the HIIT group compare to the SC group (p = 0.001). Taken together, the activity of the FoxO3a/MuRF1 pathway, but not NF-κB /MuRF1, can promote atrophy due to detraining, and MuRF1 is not always a good marker of atrophy.

Differential Responses To Heat Stress On The Regeneration Of Injured Rat Soleus And Plantaris Muscles

Differential Responses To Heat Stress On The Regeneration Of Injured Rat Soleus And Plantaris Muscles

Impacts of endurance training and crocin supplementation on the apoptotic pathways in rat skeletal muscle following doxorubicin administration

Background and aims: Doxorubicin (DOX), in addition to its anti-cancer properties, causes toxicity and increases the apoptosis of healthy tissues. The objective of the current research was to explore the concurrent influence of an eight-week aerobic training regimen combined with crocin supplementation on the apoptosis induced by DOX within the soleus muscle tissue of male rodents. Methods: In this study, a cohort of 40 male Wistar rats, each weighing between 200 and 220 g and approximately 8 weeks old, were systematically distributed into five distinct experimental clusters, including a healthy control (normal saline) and a patient control (intraperitoneal injection of 2 mg/kg of DOX ). The other clusters were DOX-exercise (intraperitoneal injection of 2 mg/kg of DOX with eight weeks of treadmill/5 days a week), DOX-crocin (intraperitoneal injection of 2 mg/kg) 2 kg of DOX along with 10 mg/kg of crocin extract/8 weeks), and DOX-exercise-crocin. Results: The administration of DOX was associated with a notable elevation in Bax and a reduction in Bcl-2 expression (P=0.001 and P=0.001). In contrast, engaging in eight weeks of aerobic exercise, ingesting crocin, or a synergistic approach combining both interventions resulted in a marked upregulation of Bcl-2 expression (P=0.001). This combined treatment also led to a significant diminution in the Bax mRNA (P=0.006) and a decrease in the Bax/Bcl-2 ratio (P=0.001) within the soleus muscle tissue of male rodents subjected to DOX exposure. Conclusion: Aerobic exercise with crocin supplementation could inhibit apoptosis caused by DOX in the soleus muscle of male rats.

Remobilization with whole-body vibration improves functionality, histomorphometric parameters, and AQP1 expression in the soleus muscle of Wistar rats.

Whole-body vibration (WBV) is used to enhance physical performance in sports and rehabilitation. The present study analyzed the effects of remobilization with WBV on the soleus muscle of Wistar rats. Twenty-eight animals were separated into four experimental groups (n = 7): CON (control); IM (immobilized); FR (immobilization and free remobilization); and WBV (immobilization and remobilization with WBV). The immobilization of the pelvic limb was carried out according to the standard protocol using a plaster cast for 15 days. For remobilization with WBV, a Frequency of 60 Hz was applied for 10 min, five days a week, for two weeks. After the remobilization period, the animals were euthanized, and the right soleus muscle was dissected followed by processing for histomorphometric analysis and immunolocalization of Aquaporin 1 (AQP1). We observed a reduced larger diameter in IM compared to CON, with restored values in WBV. For the estimation of connective tissue, a significant increase was observed in the immobilized groups, while a reduction was noted in the remobilized groups. AQP1 expression decreased significantly in IM and increased in WBV. Immobilization caused morphofunctional damage to the soleus muscle, and remobilization with WBV is efficient and offers advantages over free remobilization.

Effects of Bifidobacterium-Fermented Milk on Obesity: Improved Lipid Metabolism through Suppression of Lipogenesis and Enhanced Muscle Metabolism.

Obesity is a major global health concern. Studies suggest that the gut microflora may play a role in protecting against obesity. Probiotics, including lactic acid bacteria and Bifidobacterium, have garnered attention for their potential in obesity prevention. However, the effects of Bifidobacterium-fermented products on obesity have not been thoroughly elucidated. Bifidobacterium, which exists in the gut of animals, is known to enhance lipid metabolism. During fermentation, it produces acetic acid, which has been reported to improve glucose tolerance and insulin resistance, and exhibit anti-obesity and anti-diabetic effects. Functional foods have been very popular around the world, and fermented milk is a good candidate for enrichment with probiotics. In this study, we aim to evaluate the beneficial effects of milks fermented with Bifidobacterium strains on energy metabolism and obesity prevention. Three Bifidobacterium strains (Bif-15, Bif-30, and Bif-39), isolated from newborn human feces, were assessed for their acetic acid production and viability in milk. These strains were used to ferment milk. Otsuka-Long-Evans Tokushima Fatty (OLETF) rats administered Bif-15-fermented milk showed significantly lower weight gain compared to those in the water group. The phosphorylation of AMPK was increased and the expression of lipogenic genes was suppressed in the liver of rats given Bif-15-fermented milk. Additionally, gene expression related to respiratory metabolism was significantly increased in the soleus muscle of rats given Bif-15-fermented milk. These findings suggest that milk fermented with the Bifidobacterium strain Bif-15 can improve lipid metabolism and suppress obesity.

Force re-development after shortening reveals a role for titin in stretch-shortening performance enhancement in skinned muscle fibres.

Stretch-shortening cycles (SSCs) involve muscle lengthening (eccentric contractions) instantly followed by shortening (concentric contractions). This combination enhances force, work and power output compared with pure shortening contractions, which is known as the SSC effect. Recent evidence indicates both cross-bridge (XB)-based and non-XB-based (e.g. titin) structures contribute to this effect. This study analysed force re-development following SSCs and pure shortening contractions to gain further insight into the roles of XB and non-XB structures regarding the SSC effect. Experiments were conducted on rat soleus muscle fibres (n=16) with different SSC velocities (30%, 60% and 85% of maximum shortening velocity) and constant stretch-shortening magnitudes (18% of optimum length). The XB inhibitor blebbistatin was used to distinguish between XB and non-XB contributions to force generation. The results showed SSCs led to significantly greater [mean±s.d. 1.02±0.15 versus 0.68±0.09 (ΔF/Δt); t62=8.61, P<0.001, d=2.79) and faster (75 ms versus 205ms; t62=-6.37, P<0.001, d=-1.48) force re-development compared with pure shortening contractions in the control treatment. In the blebbistatin treatment, SSCs still resulted in greater [0.11±0.03 versus 0.06±0.01 (ΔF/Δt); t62=8.00, P<0.001, d=2.24) and faster (3010±1631 versus 7916±3230ms; t62=-8.00, P<0.001, d=-1.92) force re-development compared with pure shortening contractions. These findings deepen our understanding of the SSC effect, underscoring the involvement of non-XB structures such as titin in modulating force production. This modulation is likely to involve complex mechanosensory coupling from stretch to signal transmission during muscle contraction.

Impact of lengthening velocity on the generation of eccentric force by slow-twitch muscle fibers in long stretches

After an initial increase, isovelocity elongation of a muscle fiber can lead to diminishing (referred to as Give in the literature) and subsequently increasing force. How the stretch velocity affects this behavior in slow-twitch fibers remains largely unexplored. Here, we stretched fully activated individual rat soleus muscle fibers from 0.85 to 1.3 optimal fiber length at stretch velocities of 0.01, 0.1, and 1 maximum shortening velocity, vmax, and compared the results with those of rat EDL fast-twitch fibers obtained in similar experimental conditions. In soleus muscle fibers, Give was 7%, 18%, and 44% of maximum isometric force for 0.01, 0.1, and 1 vmax, respectively. As in EDL fibers, the force increased nearly linearly in the second half of the stretch, although the number of crossbridges decreased, and its slope increased with stretch velocity. Our findings are consistent with the concept of a forceful detachment and subsequent crossbridge reattachment in the stretch’s first phase and a strong viscoelastic titin contribution to fiber force in the second phase of the stretch. Interestingly, we found interaction effects of stretch velocity and fiber type on force parameters in both stretch phases, hinting at fiber type-specific differences in crossbridge and titin contributions to eccentric force. Whether fiber type-specific combined XB and non-XB models can explain these effects or if they hint at some not fully understood properties of muscle contraction remains to be shown. These results may stimulate new optimization perspectives in sports training and provide a better understanding of structure–function relations of muscle proteins.

Spontaneous Tonic Activity Revealed in Rat Soleus Muscle by CLP290, a Novel Spinal Cord Potassium-Chloride Cotransporter Activator, during Hindlimb Suspension

Spontaneous Tonic Activity Revealed in Rat Soleus Muscle by CLP290, a Novel Spinal Cord Potassium-Chloride Cotransporter Activator, during Hindlimb Suspension

Prazosin improves insulin-induced anabolic signaling by protecting capillary regression in the soleus muscle of hindlimb-unloaded rats

Prazosin improves insulin-induced anabolic signaling by protecting capillary regression in the soleus muscle of hindlimb-unloaded rats

Resting membrane potential and intracellular [Na+] at rest, during fatigue and during recovery in rat soleus muscle fibres in situ.

Large trans-sarcolemmal ionic shifts occur with fatiguing exercise or stimulation of isolated muscles. However, it is unknown how resting membrane potential (EM) and intracellular sodium concentration ([Na+]i) change with repeated contractions in living mammals. We investigated (i) whether [Na+]i (peak, kinetics) can reveal changes of Na+-K+ pump activity during brief or fatiguing stimulation and (ii) how resting EM and [Na+]i change during fatigue and recovery of rat soleus muscle in situ. Muscles of anaesthetised rats were stimulated with brief (10s) or repeated tetani (60Hz for 200ms, every 2s, for 30s or 300s) with isometric force measured. Double-barrelled ion-sensitive microelectrodes were used to quantify resting EM and [Na+]i. Post-stimulation data were fitted using polynomials and back-extrapolated to time zero recovery. Mean pre-stimulation resting EM (layer 2-7 fibres) was -71mV (surface fibres were more depolarised), and [Na+]i was 14mM. With deeper fibres, 10s stimulation (2-150Hz) increased [Na+]i to 38-46mM whilst simultaneously causing hyperpolarisations (7.3mV for 2-90Hz). Fatiguing stimulation for 30s or 300s led to end-stimulation resting EM of -61 to -53mV, which recovered rapidly (T1/2, 8-22s). Mean end-stimulation [Na+]i increased to 86-101mM with both fatigue protocols and the [Na+]i recovery time-course (T1/2, 21-35s) showed no difference between protocols. These combined findings suggest that brief stimulation hyperpolarises the resting EM, likely via maximum Na+-induced stimulation of the Na+-K+ pump. Repeated tetani caused massive depolarisation and elevations of [Na+]i that together lower force, although they likely interact with other factors to cause fatigue. [Na+]i recovery kinetics provided no evidence of impaired Na+-K+ pump activity with fatigue. KEY POINTS: It is uncertain how resting membrane potential, intracellular sodium concentration ([Na+]i), and sodium-potassium (Na+-K+) pump activity change during repeated muscle contractions in living mammals. For rat soleus muscle fibres in situ, brief tetanic stimulation for 10s led to raised [Na+]i, anticipated to evoke maximal Na+-induced stimulation of the Na+-K+ pump causing an immediate hyperpolarisation of the sarcolemma. More prolonged stimulation with repeated tetanic contractions causes massive elevations of [Na+]i, which together with large depolarisations (via K+ disturbances) likely reduce force production. These effects occurred without impairment of Na+-K+ pump function. Together these findings suggest that rapid activation of the Na+-K+ pump occurs with brief stimulation to maintain excitability, whereas more prolonged stimulation causes rundown of the trans-sarcolemmal K+ gradient (hence depolarisation) and Na+ gradient, which in combination can impair contraction to contribute to fatigue in living mammals.

Resveratrol impinges on retrograde communication without inducing mitochondrial biogenesis in aged rat soleus muscle

The natural polyphenol resveratrol (RSV) might counteract the skeletal muscle age-related loss of muscle mass and strength/function partly acting on mitochondria. This work analysed the effects of a six-week administration of RSV (50 mg/kg/day) in the oxidative Soleus (Sol) skeletal muscle of old rats (27 months old). RSV effects on key mitochondrial biogenesis proteins led to un unchanged amount of SIRT1 protein and a marked decrease (60 %) in PGC-1α protein. In addition, Peroxyredoxin 3 (PRXIII) protein decreased by 50 %, which on overall suggested the absence of induction of mitochondrial biogenesis by RSV in old Sol. A novel direct correlation between PGC-1α and PRXIII proteins was demonstrated by correlation analysis in RSV and ad-libitum (AL) rats, supporting the reciprocally coordinated expression of the proteins. RSV supplementation led to an unexpected 50 % increase in the frequency of the oxidized base OH8dG in mtDNA. Furthermore, RSV supplementation induced a 50 % increase in the DRP1 protein of mitochondrial dynamics. In both rat groups an inverse correlation between PGC-1α and the frequency of OH8dG as well as an inverse correlation between PRXIII and the frequency of OH8dG were also found, suggestive of a relationship between oxidative damage to mtDNA and mitochondrial biogenesis activity. Such results may indicate that the antioxidant activity of RSV in aged Sol impinged on the oxidative fiber-specific, ROS-mediated, retrograde communication, thereby affecting the expression of SIRT1, PGC-1α and PRXIII, reducing the compensatory responses to the age-related mitochondrial oxidative stress and decline.

The Effect of Aerobic Exercise and Pistachio Soft Hull Extract on the Expression of the Il-6 and IL-1β Genes in the Soleus Muscle of Female Rats Fed a High-Fat Diet

Background: Obesity is considered the most important public health problem. Previous studies have confirmed that a high-fat diet (HFD) can cause the development of systemic and tissue inflammation due to the increase in pro-inflammatory markers. Objectives: This study aims to evaluate the effect of aerobic exercise and pistachio soft hull extract (PSHE) on inflammatory gene expression in the soleus muscle of rats fed a HFD. Methods: In an experimental trial, 30 female Wistar rats weighing between 180 and 200 grams were selected as subjects and randomly divided into five groups: Normal diet control, HFD control, HFD aerobic exercise, HFD-PSHE, and HFD aerobic exercise-PSHE. The aerobic exercise program consisted of four weeks of five weekly sessions of running on a treadmill at an intensity of 50 – 60% VO2max. Pistachio soft hull extract at a dose of 60 mg/kg was administered to the rats by gavage for four weeks, five times a week. Forty-eight hours after the last interventions, the rats were anesthetized, and the soleus muscle was removed to determine the expression of the IL-6 and IL-1β genes. Results: Induction of HFD significantly decreased IL-6 (P = 0.001) and increased IL-1β (P = 0.001) gene expression. IL-1β gene expression in the aerobic exercise (P = 0.001), PSHE (P = 0.003), and aerobic exercise-PSHE (P = 0.001) groups was significantly lower than in the HFD control group. Aerobic exercise (P = 0.002), PSHE (P = 0.002), and the combination of aerobic exercise and PSHE (P = 0.003) caused a significant increase in IL-6 gene expression compared to the HFD control group. Conclusions: High-fat diet promotes inflammation in skeletal muscle by increasing the expression of the IL-1β and IL-6 genes. Aerobic exercise, PSHE, and the combination of aerobic exercise and PSHE can exert their anti-inflammatory effects by reducing the expression of the IL-1β and IL-6 genes in skeletal muscle tissue.

The relationship of sphingolipid mechanisms with oxidative stress and changes in mitochondria during functional unloading of postural muscles

Background. Prolonged inactivity of skeletal muscles is accompanied by the development of oxidative stress and changes in sphingolipid metabolism. The relationship of sphingolipid mechanisms with generation of reactive oxygen species (ROS) in muscles subjected to functional unloading has not been studied.The aim. To identify the relationship between changes in sphingomyelinase and ceramide abundance and ROS production in rat soleus muscle during functional unloading.Methods. Male Wistar rats were subjected to hindlimb suspension for 12 hours or 14 days with the acid sphingomyelinase (ASM) inhibitor amitriptyline (AMI). The levels of ASM, ceramide and ROS were determined by fluorescence microscopy on histological sections. Pro-oxidant enzymes (NADPH oxidases 2 and 4 (NOX2 and NOX4)), cytochrome c oxidase (COX IV), the regulator of mitochondrial biogenesis PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) in muscle homogenates were studied by Western blotting, which also was used for assessment of ceramide and ASM in the isolated mitochondrial fraction. The effects of sphingomyelinase and prooxidants on ceramide, ASM, ROS and NOX2 levels were studied in an ex vivo model by incubating the muscle with exogenous sphingomyelinase or H2O2.Results. 12-hour hindlimb suspension was accompanied by an increase in the level of ASM and ceramide in rat soleus muscle. Unloading for 14 days was characterized by an increase in ASM, ceramide, ROS, NOX2, NOX4 and a decrease in COX IV and PGC-1α levels. ASM and ceramide were also increased in the mitochondrial fraction of muscle. The ASM inhibitor amitriptyline partially or completely prevented the changes caused by the unloading. In the ex vivo model, the stimulating effect of exogenous sphingomyelinase on the ROS and NOX2 levels in rat soleus muscle was found, whereas H2O2 stimulated muscle ASM and ceramide production.Conclusion. A close relationship has been established between the sphingomyeli-nase pathway of ceramide formation and ROS production in skeletal muscle under conditions of functional unloading.

Investigating the Impact of Resistance Training on Myokines Gene Expression in the Skeletal Muscle of Rats

Introduction: Myokines are produced in response to contractions and mechanical stress caused by exercise and plays a key role in muscle regeneration or control of some diseases. The role of resistance training in the secretion of myokines has been less investigated. The purpose of this study was to investigate the effect of 4 weeks of resistance training on the expression of musclin, apelin and decorin genes in the soleus muscle of male Wistar rats. Methods: The present study was experimental. Sixteen 8-week-old male Wistar rats with an average weight of 223±16.99 grams were randomly divided into 2 groups of control (n=8) and resistance training (n=8). After familiarizing the animals with the laboratory environment and resistance training on the ladder, the rats in the resistance training group trained on the ladder for 4 weeks, 3 days per week. Expression values of musclin, apelin and decorin genes of soleus muscle were measured by RT-PCR method. To analyze the data, independent t test was used at the level of p&lt;0.05 using SPSS version 16 statistical software. Results: The results of this study showed that performing 4 weeks of resistance training on a regular basis can significantly increase musclin (p=0.0004), apelin (p&lt;0.0001) and decorin (p=0.0078) in the slow-twitch soleus muscle compared to the control group. Conclusion: It seems that doing resistance exercises regularly in a short period of time can significantly increase some myokines in slow-twitch muscles, which can have beneficial and preventive effects against lifestyle-related diseases.

Time-course and muscle-specific gene expression of matrix metalloproteinases and inflammatory cytokines in response to acute treadmill exercise in rats.

The extracellular matrix (ECM) of skeletal muscle plays a pivotal role in tissue repair and growth, and its remodeling tightly regulated by matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and inflammatory cytokines. This study aimed to investigate changes in the mRNA expression of MMPs (Mmp-2 and Mmp-14), TIMPs (Timp-1 and Timp-2), and inflammatory cytokines (Il-1β, Tnf-α, and Tgfβ1) in the soleus (SOL) and extensor digitorum longus (EDL) muscles of rats following acute treadmill exercise. Additionally, muscle morphology was examined using hematoxylin and eosin (H&E) staining. Male rats were subjected to acute treadmill exercise at 25m/min for 60min with a %0 slope. The mRNA expression of ECM components and muscle morphology in the SOL and EDL were assessed in both sedentary and exercise groups at various time points (immediately (0) and 1, 3, 6, 12, and 24h post-exercise). Our results revealed a muscle-specific response, with early upregulation of the mRNA expression of Mmp-2, Mmp-14, Timp-1, Timp-2, Il-1β, and Tnf-α observed in the SOL compared to the EDL. A decrease in Tgfβ1 mRNA expression was evident in the SOL at all post-exercise time points. Conversely, Tgfβ1 mRNA expression increased at 0 and 3h post-exercise in the EDL. Histological analysis also revealed earlier cell infiltration in the SOL than in the EDL following acute exercise. Our results highlight how acute exercise modulates ECM components and muscle structure differently in the SOL and EDL muscles, leading to distinct muscle-specific responses.

Exercise ameliorates muscular excessive mitochondrial fission, insulin resistance and inflammation in diabetic rats via irisin/AMPK activation

This study aimed to investigate the effects of exercise on excessive mitochondrial fission, insulin resistance, and inflammation in the muscles of diabetic rats. The role of the irisin/AMPK pathway in regulating exercise effects was also determined. Thirty-two 8-week-old male Wistar rats were randomly divided into four groups (n = 8 per group): one control group (Con) and three experimental groups. Type 2 diabetes mellitus (T2DM) was induced in the experimental groups via a high-fat diet followed by a single intraperitoneal injection of streptozotocin (STZ) at a dosage of 30 mg/kg body weight. After T2DM induction, groups were assigned as sedentary (DM), subjected to 8 weeks of treadmill exercise training (Ex), or exercise training combined with 8-week cycloRGDyk treatment (ExRg). Upon completion of the last training session, all rats were euthanized and samples of fasting blood and soleus muscle were collected for analysis using ELISA, immunofluorescence, RT-qPCR, and Western blotting. Statistical differences between groups were analyzed using one-way ANOVA, and differences between two groups were assessed using t-tests. Our findings demonstrate that exercise training markedly ameliorated hyperglycaemia, hyperlipidaemia, and insulin resistance in diabetic rats (p < 0.05). It also mitigated the disarranged morphology and inflammation of skeletal muscle associated with T2DM (p < 0.05). Crucially, exercise training suppressed muscular excessive mitochondrial fission in the soleus muscle of diabetic rats (p < 0.05), and enhanced irisin and p-AMPK levels significantly (p < 0.05). However, exercise-induced irisin and p-AMPK expression were inhibited by cycloRGDyk treatment (p < 0.05). Furthermore, the administration of CycloRGDyk blocked the effects of exercise training in reducing excessive mitochondrial fission and inflammation in the soleus muscle of diabetic rats, as well as the positive effects of exercise training on improving hyperlipidemia and insulin sensitivity in diabetic rats (p < 0.05). These results indicate that regular exercise training effectively ameliorates insulin resistance and glucolipid metabolic dysfunction, and reduces inflammation in skeletal muscle. These benefits are partially mediated by reductions in mitochondrial fission through the irisin/AMPK signalling pathway.

Effects of Alpha Lipoic Acid Supplementation on Slow Skeletal Muscle Mass and Contractile Functions in Type 2 Diabetic Male Sprague Dawley Rats

Objective: To see the Effects of Alpha-Lipoic Acid (ALA) supplementation on slow skeletal muscle mass andcontractile functions in type 2 diabetic male Sprague Dawley rats.Study Design: Quasi-experimental study.Place and Duration of Study: The study was carried out at the Physiology Research Lab, Army MedicalCollege, Rawalpindi, Pakistan from June 2019 to April 2021 in collaboration with the National Institute of Health(NIH) Islamabad, Pakistan.Methods: Sixty adult SD rats were divided into three equal groups. Rats were fed on a standard diet as per NIHprotocols. After 2 weeks type 2 Diabetes mellitus (T2DM) was induced in groups 2 and 3 by injecting low dose35mg of streptozotocin (STZ) in the abdomen intraperitoneally. T2DM was successfully developed andconfirmed by measuring glucose levels through a glucometer. Group 3 was injected with Alpha Lipoic acid30mg/kg/day at the lower abdomen for the next two weeks. After 04 weeks, soleus muscles were dissected.The animal data acquisition unit (iWorx) was used for assessing the contractile functions of soleus.Results: Alpha Lipoic acid group showed improvement in muscle mass, muscle tension strength, and recoveryfrom fatigue after applying fatigue protocol as compared to group 2.Conclusion: Alpha Lipoic acid supplementation improves contractile force and delays fatigue in the soleusmuscles of diabetic rats. How to cite this: Khan BU, Yousef I, Arshad S, Ikram F, Ali A, Ullah I. Effects of Alpha Lipoic Acid Supplementation on Slow Skeletal Muscle Mass and Contractile Functions in Type 2 Diabetic Male Sprague Dawley Rats. Life and Science. 2024; 5(2): 216-221. doi: http://doi.org/10.37185/LnS.1.1.408

Sa1943 MECHANOKINETICS OF MUSCLE FATIGUE DEVELOPMENT IN SOLEUS MUSCLES OF OBESE RATS

Sa1943 MECHANOKINETICS OF MUSCLE FATIGUE DEVELOPMENT IN SOLEUS MUSCLES OF OBESE RATS

Characterization of Skeletal Muscle Regeneration Revealed a Novel Growth Network Induced by Molecular Acupuncture-like Transfection.

The low efficiency of in vivo transfection of a few fibres revealed a novel tissue network that temporally amplified growth stimulation in the entire regenerating rat soleus muscle. This acupuncture-like effect was demonstrated when the fibres began to grow after complete fibre degradation, synchronous inflammation, myoblast and myotube formation. Neonatal sarcoplasmic/endoplasmic reticulum ATPase (SERCA1b) was first detected in this system. The neonatal, fast and slow SERCA isoforms displayed consequent changes with innervation and differentiation, recapitulating events in muscle development. In vivo transfection of myotubes with plasmids expressing dominant negative Ras or a calcineurin inhibitor peptide (Cain/cabin) proved that expression of the slow myosin heavy chain and the slow muscle type SERCA2a are differentially regulated. In vivo transfection of a few nuclei of myotubes with dnRas or SERCA1b shRNA stimulated fibre size growth in the whole regenerating muscle but only until the full size had been reached. Growth stimulation by Ras and SERCA1b antisense was abolished by co-transfection of Cain or with perimuscular injection of IL4 antibody. This revealed a novel signalling network resembling scale-free networks which, starting from transfected fibre myonuclei as "hubs", can amplify growth stimulation uniformly in the entire regenerating muscle.