Neural regulation of the enhanced uptake of glucose in skeletal muscle after endotoxin

1995 ◽  
Vol 269 (2) ◽  
pp. R437-R444 ◽  
Author(s):  
C. H. Lang
Keyword(s):  
Skeletal Muscle ◽  
Nerve Transection ◽  
Muscle Denervation ◽  
Denervated Muscle ◽  
Muscle Type ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Sciatic Nerve Transection ◽  
Insulin Levels ◽  
Stimulation Of

Previous studies have demonstrated that in vivo injection of lipopolysaccharide (LPS) acutely stimulates glucose uptake (GU) in skeletal muscle. The purpose of the present study was to determine whether this enhanced GU is neurally mediated. In the first group of rats, a unilateral sciatic nerve transection was performed 3 h before injection of LPS, and in vivo GU was assessed using 2-[14C]deoxy-D-glucose 40 min after LPS injection. At this time, LPS-treated rats were hyperglycemic (12 mM), and insulin levels were not different from control rats. In the innervated leg, LPS increased GU 43-228%, depending on the muscle type. In contrast, LPS failed to increase GU in muscles from the denervated limb. In other experiments, somatostatin was infused to produce an insulinopenic condition before the injection of LPS. Despite insulinopenia, muscle GU was still increased by LPS. In control rats, in which the euglycemic hyperinsulinemic clamp technique was used, acute muscle denervation was shown to impair insulin-mediated GU in the presence of pharmacological, but not physiological, insulin levels. Non-insulin-mediated GU (NIMGU) was assessed in rats that were insulinopenic and hyperglycemic. In innervated muscle, NIMGU was increased 56-126 and 118-145% when the plasma glucose was elevated to 9 and 12 mM, respectively. In contrast, hyperglycemia-induced increases in NIMGU were attenuated in denervated muscle. These data demonstrate that 1) the early LPS-induced stimulation of muscle GU is mediated via a non-insulin-mediated pathway and 2) the LPS-induced increase in NIMGU in muscle is neurally mediated.

Phospholipids, prostaglandin E2, and proteolysis in denervated muscle

1986 ◽  
Vol 251 (1) ◽  
pp. R165-R173 ◽  
Author(s):  
J. Turinsky
Keyword(s):  
Protein Synthesis ◽  
Prostaglandin E2 ◽  
Pge2 Production ◽  
Nerve Transection ◽  
Denervated Muscle ◽  
Sciatic Nerve Transection ◽  
Tissue Protein ◽  
Pge2 Release ◽  
Denervated Muscles

Soleus muscles of rats were studied up to 16 days after sciatic nerve transection. At the end of this period the denervated soleus muscles exhibited decreased content of diphosphatidylglycerol (-44%), normal level of phosphatidylethanolamine, and increased contents of phosphatidylcholine (+24%), sphingomyelin (+48%), lysophosphatidylcholine (+110%), phosphatidylinositol (+37%), and phosphatidylserine (+40%) per milligram of tissue protein. In studies in vitro, prostaglandin E2 (PGE2) release and tyrosine release by denervated soleus muscles were 319 and 141%, respectively, greater than those of sham muscles. An almost complete inhibition of PGE2 release with 5 X 10(-4) M aspirin or 2.8 X 10(-6) M indomethacin had no effect on tyrosine release of sham muscles or the stimulated tyrosine release of the denervated muscles. Addition of 5 X 10(-5) M cycloheximide in the medium resulted in 63% inhibition of PGE2 release by both groups of muscles; concomitant absolute increments in tyrosine releases by denervated and sham muscles did not statistically differ. In the presence of both 5 X 10(-5) M cycloheximide and 5 X 10(-4) M aspirin in the medium, PGE2 production by denervated and sham muscles was inhibited 87% while tyrosine release of denervated muscles was 108% higher than that of sham animals. It is concluded that 1) atrophy of denervated soleus muscle is associated with stimulated activity of tissue phospholipase A2, increased production of prostaglandin E2, increased total proteolytic rate, and unchanged rate of protein synthesis; 2) acute inhibition of PGE2 production does not inhibit the stimulated proteolysis in denervated muscle; and 3) cycloheximide inhibits PGE2 production by muscle.

Mechanisms of Pi regulation of the skeletal muscle SR Ca2+ release channel

2000 ◽  
Vol 278 (3) ◽  
pp. C601-C611 ◽  
Author(s):  
Edward M. Balog ◽  
Bradley R. Fruen ◽  
Patricia K. Kane ◽  
Charles F. Louis
Keyword(s):  
Skeletal Muscle ◽  
Single Channel ◽  
Adenine Nucleotides ◽  
Muscle Fibers ◽  
Open Probability ◽  
Release Channel ◽  
High Concentrations ◽  
Channel Open Time ◽  
Stimulation Of

Inorganic phosphate (Pi) accumulates in the fibers of actively working muscle where it acts at various sites to modulate contraction. To characterize the role of Pi as a regulator of the sarcoplasmic reticulum (SR) calcium (Ca2+) release channel, we examined the action of Pi on purified SR Ca2+ release channels, isolated SR vesicles, and skinned skeletal muscle fibers. In single channel studies, addition of Pi to the cis chamber increased single channel open probability ( P o; 0.079 ± 0.020 in 0 Pi, 0.157 ± 0.034 in 20 mM Pi) by decreasing mean channel closed time; mean channel open times were unaffected. In contrast, the ATP analog, β,γ-methyleneadenosine 5′-triphosphate (AMP-PCP), enhanced P o by increasing single channel open time and decreasing channel closed time. Pi stimulation of [3H]ryanodine binding by SR vesicles was similar at all concentrations of AMP-PCP, suggesting Pi and adenine nucleotides act via independent sites. In skinned muscle fibers, 40 mM Pi enhanced Ca2+-induced Ca2+ release, suggesting an in situ stimulation of the release channel by high concentrations of Pi. Our results support the hypothesis that Pi may be an important endogenous modulator of the skeletal muscle SR Ca2+ release channel under fatiguing conditions in vivo, acting via a mechanism distinct from adenine nucleotides.

Fatty Acid Oxidation by Skeletal Muscle During Rest and Activity

1958 ◽  
Vol 194 (2) ◽  
pp. 379-386 ◽  
Author(s):  
Irving B. Fritz ◽  
Don G. Davis ◽  
Robert H. Holtrop ◽  
Harold Dundee
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Palmitic Acid ◽  
Fatty Acid Oxidation ◽  
Latissimus Dorsi ◽  
Acid Metabolism ◽  
Fat Metabolism ◽  
Acid Oxidation ◽  
Stimulation Of

The metabolism of C14-labeled acetate, octanoate and palmitate by isolated skeletal muscle (latissimus dorsi and diaphragm) from normal, fed rats has been examined. The rates at which these substrates were converted to C14O2 have been shown to vary with concentration, temperature, functional state of the muscle, and the presence of albumin. Increased concentration of fatty acids led to enhanced conversion of substrate to C14O2. Electrical stimulation of muscles under tension resulted in approximately a 60% increase in oxygen consumption and about a 100% rise in fatty acid oxidation. The addition of glucose did not alter the rate of fatty acid metabolism by muscle. The addition of bovine albumin at concentrations up to approximately 1 µm albumin/7 µm palmitate resulted in augmented palmitic acid oxidation. However, at concentrations of albumin greater than 1 µm albumin/7 µm palmitate, palmitic acid degradation by resting diaphragm was inhibited, suggesting a firmer binding of fatty acid to albumin. The Q10 for palmitic acid oxidation by resting diaphragm was 2.23 in the absence of added albumin between 25° and 37°C. The data are discussed in relation to the present concepts of fat metabolism and transport in vivo. It is suggested that fat degradation in isolated muscle may provide an energy source during activity.

scholarly journals Skeletal muscle denervation investigations: selecting an experimental control wisely

2019 ◽  
Vol 316 (3) ◽  
pp. C456-C461 ◽  
Author(s):  
Haiming Liu ◽  
LaDora V. Thompson
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Tibial Nerve ◽  
Nerve Transection ◽  
Muscle Denervation ◽  
Crossover Effect ◽  
Proteolytic System ◽  
Experimental Control ◽  
Denervated Muscles

Unilateral denervation is widely used for studies investigating mechanisms of muscle atrophy. The “contralateral-innervated muscle” is a commonly used experimental control in denervation studies. It is not clear whether denervation unilaterally alters the proteolytic system in the contralateral-innervated muscles. Therefore, the objectives of this rapid report are 1) to determine whether unilateral denervation has an effect on the proteolytic system in contralateral-innervated control muscles and 2) to identify the changes in proteasome properties in denervated muscles after 7- and 14-day tibial nerve transection with either the contralateral-innervated muscles or intact muscles from nonsurgical mice used as the experimental control. In the contralateral-innervated muscles after 7 and 14 days of nerve transection, the proteasome activities and content are significantly increased compared with muscles from nonsurgical mice. When the nonsurgical mice are used as the experimental control, a robust increase in proteasome properties is found in the denervated muscles. This robust increase in proteasome properties is eliminated when the contralateral-innervated muscles are the experimental control. In conclusion, there is a crossover effect from unilateral denervation on proteolytic parameters. As a result, the crossover effect on contralateral-innervated muscles must be considered when an experimental control is selected in a denervation study.

scholarly journals Optogenetic activation of muscle contraction in vivo

2020 ◽  
Author(s):  
Elahe Ganji ◽  
C. Savio Chan ◽  
Christopher W. Ward ◽  
Megan L. Killian
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Muscle Contraction ◽  
Fluorescent Imaging ◽  
Triceps Surae ◽  
Light Activation ◽  
Non Invasive ◽  
Optogenetic Stimulation ◽  
Stimulation Of

AbstractOptogenetics is an emerging alternative to traditional electrical stimulation to initiate action potentials in activatable cells both ex vivo and in vivo. Optogenetics has been commonly used in mammalian neurons and more recently, it has been adapted for activation of cardiomyocytes and skeletal muscle. Therefore, the aim of this study was to evaluate the stimulation feasibility and sustain isometric muscle contraction and limit decay for an extended period of time (1s), using non-invasive transdermal light activation of skeletal muscle (triceps surae) in vivo. We used inducible Cre recombination to target expression of Channelrhodopsin-2 (ChR2(H134R)-EYFP) in skeletal muscle (Acta1-Cre) in mice. Fluorescent imaging confirmed that ChR2 expression is localized in skeletal muscle and does not have specific expression in sciatic nerve branch, therefore, allowing for non-nerve mediated optical stimulation of skeletal muscle. We induced muscle contraction using transdermal exposure to blue light and selected 10Hz stimulation after controlled optimization experiments to sustain prolonged muscle contraction. Increasing the stimulation frequency from 10Hz to 40Hz increased the muscle contraction decay during prolonged 1s stimulation, highlighting frequency dependency and importance of membrane repolarization for effective light activation. Finally, we showed that optimized pulsed optogenetic stimulation of 10 Hz resulted in comparable ankle torque and contractile functionality to that of electrical stimulation. Our results demonstrate the feasibility and repeatability of non-invasive optogenetic stimulation of muscle in vivo and highlight optogenetic stimulation as a powerful tool for non-invasive in vivo direct activation of skeletal muscle.

Cytosolic citrate and malonyl-CoA regulation in rat muscle in vivo

1999 ◽  
Vol 276 (6) ◽  
pp. E1030-E1037 ◽  
Author(s):  
Asish K. Saha ◽  
D. Ross Laybutt ◽  
David Dean ◽  
Demetrios Vavvas ◽  
Elena Sebokova ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Plasma Insulin ◽  
Fatty Acyl ◽  
Rat Skeletal Muscle ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Whole Cell ◽  
Rat Muscle ◽  
Malonyl Coa ◽  
Cell Concentrations

In liver, insulin and glucose acutely increase the concentration of malonyl-CoA by dephosphorylating and activating acetyl-CoA carboxylase (ACC). In contrast, in incubated rat skeletal muscle, they appear to act by increasing the cytosolic concentration of citrate, an allosteric activator of ACC, as reflected by increases in the whole cell concentrations of citrate and malate [Saha, A. K., D. Vavvas, T. G. Kurowski, A. Apazidis, L. A. Witters, E. Shafrir, and N. B. Ruderman. Am. J. Physiol. 272 ( Endocrinol. Metab. 35): E641–E648, 1997]. We report here that sustained increases in plasma insulin and glucose may also increase the concentration of malonyl-CoA in rat skeletal muscle in vivo by this mechanism. Thus 70 and 125% increases in malonyl-CoA induced in skeletal muscle by infusions of glucose for 1 and 4 days, respectively, and a twofold increase in its concentration during a 90-min euglycemic-hyperinsulinemic clamp were all associated with significant increases in the sum of whole cell concentrations of citrate and/or malate. Similar correlations were observed in muscle of the hyperinsulinemic fa/fa rat, in denervated muscle, and in muscle of rats infused with insulin for 5 h. In muscle of 48-h-starved rats 3 and 24 h after refeeding, increases in malonyl-CoA were not accompanied by consistent increases in the concentrations of malate or citrate. However, they were associated with a decrease in the whole cell concentration of long-chain fatty acyl-CoA (LCFA-CoA), an allosteric inhibitor of ACC. The results suggest that increases in the concentration of malonyl-CoA, caused in rat muscle in vivo by sustained increases in plasma insulin and glucose or denervation, may be due to increases in the cytosolic concentration of citrate. In contrast, during refeeding after starvation, the increase in malonyl-CoA in muscle is probably due to another mechanism.

Insulin resistance in polycystic ovary syndrome is associated with defective regulation of ERK1/2 by insulin in skeletal muscle in vivo

2009 ◽  
Vol 418 (3) ◽  
pp. 665-671 ◽  
Author(s):  
Madhurima Rajkhowa ◽  
Sandra Brett ◽  
Daniel J. Cuthbertson ◽  
Christopher Lipina ◽  
Antonio J. Ruiz-Alcaraz ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Insulin Signalling ◽  
Polycystic Ovary ◽  
Insulin Stimulation ◽  
Ovary Syndrome ◽  
Stimulation Of

Insulin resistance is a recognized feature of PCOS (polycystic ovary syndrome). However, the molecular reason(s) underlying this reduced cellular insulin sensitivity is not clear. The present study compares the major insulin signalling pathways in skeletal muscle isolated from PCOS and controls. We measured whole-body insulin sensitivity and insulin signalling in skeletal muscle biopsies taken before and after acute exposure to hyperinsulinaemia in nine women diagnosed with PCOS and seven controls. We examined the expression, basal activity and response to in vivo insulin stimulation of three signalling molecules within these human muscle samples, namely IRS-1 (insulin receptor substrate-1), PKB (protein kinase B) and ERK (extracellular-signal-regulated kinase) 1/2. There was no significant difference in the expression, basal activity or activation of IRS-1 or PKB between PCOS and control subjects. However, there was a severe attenuation of insulin stimulation of the ERK pathway in muscle from all but two of the women with PCOS (the two most obese), and an accompanying trend towards higher basal phosphorylation of ERK1/2 in PCOS. These results are striking in that the metabolic actions of insulin are widely believed to require the IRS-1/PKB pathway rather than ERK, and the former has been reported as defective in some previous PCOS studies. Most importantly, the molecular defect identified was independent of adiposity. The altered response of ERK to insulin in PCOS was the most obvious signalling defect associated with insulin resistance in muscle from these patients.

γ-Acetylcholine Receptor Mediating Dynamic Changes of Resistance to Rocuronium in the Denervated Skeletal Muscle

Pharmacology ◽  
2018 ◽  
Vol 102 (3-4) ◽  
pp. 190-195 ◽  
Author(s):  
Hong Wang ◽  
Wei Fu ◽  
Lian-hua Chen ◽  
Shi-tong Li
Keyword(s):  
Skeletal Muscle ◽  
Acetylcholine Receptor ◽  
Pearson Correlation ◽  
Muscle Relaxants ◽  
Muscle Denervation ◽  
Denervated Muscle ◽  
Dynamic Changes ◽  
Ic50 Values ◽  
Pearson Correlation Analysis ◽  
The Relationship

Background/Aims: Denervation resulted in resistance to non-depolarizing muscle relaxants (NDMRs), the magnitude of which changed after denervation in the skeletal muscle. The aim of this study was to investigate whether changed potencies of rocuronium were due to altered γ-acetylcholine receptor (γ-AChR) expression after skeletal muscle denervation. Methods: Innervated and denervated muscle cells were used in this study. Patch clamp and Western blotting techniques were separately applied to examine IC50 values of rocuronium and γ-AChR protein expression at different times after denervation. Then, using the linear Pearson correlation analysis, the relationship between IC50 values of rocuronium and γ-AChR expression was tested. Results: Compared with the innervated control, both IC50 values of rocuronium and γ-AChR expression significantly increased at Day 4, 7, and 14 after denervation in the skeletal muscle. Furthermore, γ-AChR protein and IC50 values of rocuronium exibited a significant positive correlation (r = 0.7678, p < 0.0001). Conclusion: These above results indicated that dynamic changes of resistance to NDMRs may be due to altered γ-AChR expression after skeletal muscle denervation.

scholarly journals Fibroblasts that proliferate near denervated synaptic sites in skeletal muscle synthesize the adhesive molecules tenascin(J1), N-CAM, fibronectin, and a heparan sulfate proteoglycan.

1989 ◽  
Vol 108 (5) ◽  
pp. 1873-1890 ◽  
Author(s):  
C L Gatchalian ◽  
M Schachner ◽  
J R Sanes
Keyword(s):  
Skeletal Muscle ◽  
Heparan Sulfate ◽  
Heparan Sulfate Proteoglycan ◽  
Sulfate Proteoglycan ◽  
3T3 Cells ◽  
Denervated Muscle ◽  
Electron Microscopic ◽  
Cultured Fibroblasts ◽  
Adhesive Molecules

Four adhesive molecules, tenascin(J1), N-CAM, fibronectin, and a heparan sulfate proteoglycan, accumulate in interstitial spaces near synaptic sites after denervation of rat skeletal muscle (Sanes, J. R., M. Schachner, and J. Covault. 1986. J. Cell Biol. 102:420-431). We have now asked which cells synthesize these molecules, and how this synthesis is regulated. Electron microscopy revealed that mononucleated cells selectively accumulate in perisynaptic interstitial spaces beginning 2 d after denervation. These cells were identified as fibroblasts by ultrastructural and immunohistochemical criteria; [3H]thymidine autoradiography revealed that their accumulation results from local proliferation. Electron microscopic immunohistochemistry demonstrated that N-CAM is associated with the surface of the fibroblasts, while tenascin(J1) is associated with collagen fibers that abut fibroblasts. Using immunofluorescence and immunoprecipitation methods, we found that fibroblasts isolated from perisynaptic regions of denervated muscle synthesize N-CAM, tenascin(J1), fibronectin, and a heparan sulfate proteoglycan in vitro. Thus, fibroblasts that selectively proliferate in interstitial spaces near synaptic sites are likely to be the cellular source of the interstitial deposits of adhesive molecules in denervated muscle. To elucidate factors that might regulate the accumulation of these molecules in vivo, we analyzed the expression of tenascin(J1) and fibronectin by cultured fibroblasts. Fibroblasts from synapse-free regions of denervated muscle, as well as skin, lung, and 3T3 fibroblasts accumulate high levels of tenascin(J1) and fibronectin in culture, showing that perisynaptic fibroblasts are not unique in this regard. However, when they are first placed in culture, fibroblasts from denervated muscle bear more tenascin(J1) than fibroblasts from innervated muscle, indicating that expression of this molecule by fibroblasts is regulated by the muscle's state of innervation; this difference is no longer apparent after a few days in culture. In 3T3 cells, accumulation of tenascin(J1) is high in proliferating cultures, depressed in confluent cultures, and reactivated in cells stimulated to proliferate by replating at low density or by wounding a confluent monolayer. Thus, synthesis of tenascin(J1) is regulated in parallel with mitotic activity. In contrast, levels of fibronectin, which increase less dramatically after denervation in vivo, are similar in fibroblasts from innervated and denervated muscle and in proliferating and quiescent 3T3 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Phenylarsine oxide and denervation effects on hormone-stimulated glucose transport

1988 ◽  
Vol 255 (2) ◽  
pp. E159-E165 ◽  
Author(s):  
M. O. Sowell ◽  
K. A. Robinson ◽  
M. G. Buse
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Insulin Action ◽  
Denervated Muscle ◽  
Phenylarsine Oxide ◽  
Early Step ◽  
Factor I ◽  
Igf I ◽  
Receptor Number ◽  
Stimulation Of

Insulin and insulin-like growth factor I (IGF-I) stimulate glucose transport in skeletal muscle through separate receptors. The proximal postreceptor events in coupling insulin and IGF-I receptors to glucose transport have been suggested to differ. Denervation of skeletal muscle produces a postreceptor insulin resistance presumably at an early step in the signaling cascade. We examined the effects of denervation and phenylarsine oxide (PAO), an agent believed to block insulin action on transport at a postreceptor step, on insulin and IGF-I stimulated 2-deoxy-D-glucose transport in isolated solei. Denervation (24 h) produced severe IGF-I resistance without affecting IGF-I receptor number or affinity. PAO inhibited insulin and IGF-I stimulation of transport in control muscles by approximately 90 and approximately 70%, respectively. In denervated muscle PAO inhibited transport stimulation by both hormones less than in controls. Conclusions are that 1) skeletal muscle insulin and IGF-I receptors signal transport mainly through a PAO-sensitive mechanism, but IGF-I's action involves a larger PAO-resistant component; 2) the denervation-induced postreceptor resistance of glucose transport to both hormones involves primarily the PAO-sensitive pathway.

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