Comparative study on muscle function in two different streptozotocin-induced diabetic models.

Aims: Streptozotocin (STZ) is widely used to study diabetic complications. Owing to the nonspecific cytotoxicity of high-dose STZ, alternative models using moderate-dose or a combination of low-dose STZ and a high-fat diet have been established. This study aimed to investigate the effects of these models on muscle function.

GDE5/Gpcpd1 activity determines phosphatidylcholine composition in skeletal muscle and regulates contractile force in mice.

Glycerophosphocholine (GPC) is an important precursor for intracellular choline supply in phosphatidylcholine (PC) metabolism. GDE5/Gpcpd1 hydrolyzes GPC into choline and glycerol 3-phosphate; this study aimed to elucidate its physiological function in vivo. Heterozygous whole-body GDE5-deficient mice reveal a significant GPC accumulation across tissues, while homozygous whole-body knockout results in embryonic lethality.

Arginine ingestion inhibits phagocyte invasion in eccentrically contracted rat fast-twitch muscle.

Eccentric contraction (ECC) has been shown to induce leukocyte invasion into skeletal muscle, resulting in muscle inflammation. This study aimed to investigate whether prior ingestion of L-arginine (ARG), a nitric oxide precursor, inhibits ECC-induced macrophage invasion. Male Wistar rats received ARG in water for 7 days, beginning 3 days prior to ECC.

Effects of eccentric contraction on force enhancement in rat fast-twitch muscle.

The aim of this study was to elucidate the effects of eccentric contraction (ECC) on force enhancement in rat fast-twitch skeletal muscle. Gastrocnemius (GAS) muscles were subjected to 200 ECCs in situ by electrical stimulation. Immediately before and after the stimulation, isometric torque produced by ankle flexion was measured at an ankle angle of 90°.

Effects of Leucine Ingestion and Contraction on the Sestrin/GATOR2 Pathway and mTORC1 Activation in Rat Fast-Twitch muscle.

Background: Leucine activates the mechanistic/mammalian target of rapamycin complex 1 (mTORC1) in mammalian skeletal muscle. Recent studies have shown that Sestrin, a leucine sensor, might play a role in this process. However, it remains unknown whether Sestrin dissociates from GATOR2 in a dose- and time-dependent manner and whether an acute bout of muscle contraction augments this dissociation.

Glutathione depression alters cellular mechanisms of skeletal muscle fatigue in early stage of recovery and prolongs force depression in late stage of recovery.

The effects of reduced glutathione (GSH) on skeletal muscle fatigue were investigated. GSH was depressed by buthionine sulfoximine (BSO) (100 mg/kg body wt/day) treatment for 5 days, which decreased GSH content to ∼10%. Male Wistar rats were assigned to the control ( = 18) and BSO groups ( = 17).

Eccentric muscle contraction potentiates titin stiffness-related contractile properties in rat fast-twitch muscles.

This study was conducted to examine the effects of an acute bout of eccentric muscle contraction (ECC) on titin stiffness-related contractile properties in rat fast-twitch skeletal muscles. Intact gastrocnemius muscles were electrically stimulated in situ to undergo 200 repeated ECCs. Immediately after the cessation of the stimulation, the superficial regions of the muscles were dissected and subjected to biochemical and skinned fiber analyses.

Mechanisms of eccentric contraction-induced muscle damage and nutritional supplementations for mitigating it.

Eccentric contraction (ECC) often results in large and long-lasting force deficits accompanied by muscle soreness, primarily due to muscle damage. In this sense, exercises that involve ECC are less desirable. Paradoxically, exercise training that includes a substantial eccentric phase leads to a more powerful activation of the genes responsible for skeletal muscle remodeling (e.

[How to evaluate skeletal muscle function: suggestion from studies on skeletal muscle fatigue].

In studies on skeletal muscle, an in vitro force measurement has been widely used to evaluate its function. However, it is recently suggested that in some cases, the results obtained by such measurement do not necessarily reflect the force in vivo, because the measurement has some disadvantages. For example, the muscles are contracted under different conditions from in vivo and there is no blood flow.

Effects of vigorous isometric muscle contraction on titin stiffness-related contractile properties in rat fast-twitch muscles.

This study was conducted to examine the effects of an acute bout of vigorous isometric contractions on titin stiffness-related contractile properties in rat fast-twitch skeletal muscles. Intact gastrocnemius muscles were electrically stimulated in situ until the force was reduced to ∼50% of the initial force. Immediately after cessation of the stimulation, the superficial regions of the muscles were dissected and subjected to biochemical and skinned fiber analyses.

Orthograde signal of dihydropyridine receptor increases Ca leakage after repeated contractions in rat fast-twitch muscles in vivo.

The purpose of this study was to investigate the mechanism underlying sarcoplasmic reticulum (SR) Ca leakage after in vivo contractions. Rat gastrocnemius muscles were electrically stimulated in vivo, and then mechanically skinned fibers and SR microsomes were prepared from the muscles excised 30 min after repeated high-intensity contractions. The mechanically skinned fibers maintained the interaction between dihydropyridine receptors (DHPRs) and ryanodine receptors (RyRs), whereas the SR microsomes did not.

Fatigue-induced change in T-system excitability and its major cause in rat fast-twitch skeletal muscle in vivo.

Key Points: Using mechanically skinned rat muscle fibres, we investigated (i) transverse tubular-system (T-system) excitability after high-intensity contractions, and (ii) the mechanisms underlying the fatigue-induced alteration of the T-system excitability. T-system excitability estimated by using skinned fibres, which is highly regulated by T-system Na -K -ATPase, was decreased after muscle contractions, but was fully restored by treatment with dithiothreitol. The S-glutathionylation of Na -K -ATPase in whole muscle was increased after muscle contractions and also occurred under very low ATP conditions in rested but not stimulated fibres.

Effects of high-intensity interval exercise on muscle fatigue and SR function in rats: a comparison with moderate-intensity continuous exercise.

In this study, we compared muscle fatigue induced by high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE), with a focus on changes in the function of sarcoplasmic reticulum (SR) and myofibril. To achieve the aim of this study with mechanically skinned fibers with sealed transverse tubules and intact SR membrane, myofibrillar Ca sensitivity, depolarization-induced force, and action potential-induced force were evaluated. Rat gastrocnemius muscles were subjected to HIIE-mimicking or MICE-mimicking stimulation in situ.

Effects of reduced muscle glycogen on excitation-contraction coupling in rat fast-twitch muscle: a glycogen removal study.

The aim of this study was to investigate the effects of an enzymatic removal of glycogen on excitation-contraction coupling in mechanically skinned fibres of rat fast-twitch muscles, with a focus on the changes in the function of Na-K-pump and ryanodine receptor (RyR). Glycogen present in the skinned fibres and binding to microsomes was removed using glucoamylase (GA). Exposure of whole muscle to 20 U mL GA for 6 min resulted in a 72% decrease in the glycogen content.

Treatment with EUK-134 improves sarcoplasmic reticulum Ca release but not myofibrillar Ca sensitivity after fatiguing contraction of rat fast-twitch muscle.

Skeletal muscles undergoing vigorous activity can enter a state of prolonged low-frequency force depression (PLFFD). This study was conducted to examine whether antioxidant treatment is capable of accelerating the recovery from PLFFD, with a focus on the function of the sarcoplasmic reticulum (SR) and myofibril. One hour before fatiguing stimulation (FS) was administered, rats received an intraperitoneal injection of Eukarion (EUK-134), which mimics the activities of superoxide dismutase and catalase.

Ingestion of soy protein isolate attenuates eccentric contraction-induced force depression and muscle proteolysis via inhibition of calpain-1 activation in rat fast-twitch skeletal muscle.

Objective: Eccentric contraction (ECC) is a contraction in which skeletal muscles are stretched while contracting. The aim of this study was to determine how ingestion of soy protein isolate (SPI) or animal-based proteins affect force deficit, calpain activation, and proteolysis of calcium ion (Ca)-regulatory proteins in rat fast-twitch muscles subjected to ECC.

Methods: In the first experiment, male Wistar rats were randomly assigned to a control and an SPI group, which were fed a 20% casein and a 20% SPI diet, respectively, for 28 d before the ECC protocol.

Thermal pretreatment facilitates recovery from prolonged low-frequency force depression in rat fast-twitch muscle.

The aim of this study was to examine whether thermal pretreatment can accelerate recovery from prolonged low-frequency force depression. The hindlimbs of thermal treated (T-treated) rats were immersed in water heated to 42.0°C for 20 min (thermal pretreatment).

Electrical Stimulation Prevents Preferential Skeletal Muscle Myosin Loss in Steroid-Denervation Rats.

Severe muscle weakness concomitant with preferential depletion of myosin has been observed in several pathological conditions. Here, we used the steroid-denervation (S-D) rat model, which shows dramatic decrease in myosin content and force production, to test whether electrical stimulation (ES) treatment can prevent these deleterious changes. S-D was induced by cutting the sciatic nerve and subsequent daily injection of dexamethasone for 7 days.

Preconditioning contractions prevent the delayed onset of myofibrillar dysfunction after damaging eccentric contractions.

Key Points: We examined the mechanisms underlying the positive effect of preconditioning contractions (PCs) on the recovery of muscle force after damaging eccentric contractions (ECCs). The mechanisms underlying the immediate force decrease after damaging ECCs differ from those causing depressed force with a few days' delay, where reactive oxygen species (ROS) produced by invading immune cells play an important causative role. PCs counteracted the delayed onset force depression and this could be explained by prevention of immune cell invasion, which resulted in decreased myeloperoxidase-mediated ROS production, hence avoiding cell membrane disruption, calpain activation and degenerative changes in myosin and actin molecules.

l-arginine ingestion inhibits eccentric contraction-induced proteolysis and force deficit via S-nitrosylation of calpain.

It has been shown that calpains are involved in the proteolysis of muscle proteins that occurs with eccentric contraction (ECC) and that exogenously applied nitric oxide decreases the calpain-mediated proteolysis. The aim of this study was to examine the effects of ingestion of l-arginine (ARG), a nitric oxide precursor, on ECC-related calpain activation. In the first and second experiments, male Wistar rats were given ARG in water for 7 days starting from 3 days before the ECC protocol (average ingestion, ~600 mg kg-body wt  day ).

Neuromuscular electrical stimulation prevents skeletal muscle dysfunction in adjuvant-induced arthritis rat.

Skeletal muscle weakness is a prominent feature in patients with rheumatoid arthritis (RA). In this study, we investigated whether neuromuscular electrical stimulation (NMES) training protects against skeletal muscle dysfunction in rats with adjuvant-induced arthritis (AIA). AIA was produced by intraarticular injection of complete Freund's adjuvant into the knees of Wistar rats.

Role of calpain in eccentric contraction-induced proteolysis of Ca-regulatory proteins and force depression in rat fast-twitch skeletal muscle.

The aim of this study was to examine the in vivo effects of eccentric contraction (ECC) on calpain-dependent proteolysis of Ca-regulatory proteins and force production in fast-twitch skeletal muscles. Rat extensor digitorum longus muscles were exposed to 200 repeated ECC in situ and excised immediately [recovery 0 (REC0)] or 3 days [recovery 3 (REC3)] after cessation of ECC. Calpain inhibitor (CI)-treated rats were intraperitoneally injected with MDL-28170 before ECC and during REC3.

Predominant cause of prolonged low-frequency force depression changes during recovery after in situ fatiguing stimulation of rat fast-twitch muscle.

To investigate time-dependent changes in sarcoplasmic reticulum (SR) Ca release and myofibrillar (my-) Ca sensitivity during recovery from prolonged low-frequency force depression (PLFFD), rat gastrocnemius muscles were electrically stimulated in situ. After 0 h (R0), 0.5 h (R0.

Time Course Analysis of Skeletal Muscle Pathology of GDE5 Transgenic Mouse.

Glycerophosphodiesterase 5 (GDE5) selectively hydrolyses glycerophosphocholine to choline and is highly expressed in type II fiber-rich skeletal muscles. We have previously generated that a truncated mutant of GDE5 (GDE5dC471) that lacks phosphodiesterase activity and shown that transgenic mice overexpressing GDE5dC471 in skeletal muscles show less skeletal muscle mass than control mice. However, the molecular mechanism and pathophysiological features underlying decreased skeletal muscle mass in GDE5dC471 mice remain unclear.

Muscle dysfunction associated with adjuvant-induced arthritis is prevented by antioxidant treatment.

Background: In addition to the primary symptoms arising from inflamed joints, muscle weakness is prominent and frequent in patients with rheumatoid arthritis (RA). Here, we investigated the mechanisms of arthritis-induced muscle dysfunction in rats with adjuvant-induced arthritis (AIA).

Methods: AIA was induced in the knees of rats by injection of complete Freund's adjuvant and was allowed to develop for 21 days.